Bio

Publications


2020

Derese, S.  2020.  Flavonoids and Isoflavonoids of Millettia dura and Millettia ferruginea: Phytochemical review and chemotaxonomic values. Biochemical Systematics and Ecology. 91 Abstract

The phytochemical information on Millettia dura Dunn, M. ferruginea (Hochst.) Baker and M. ferruginea subsp. darassana (Cufod.) J.B. Gillett was reviewed. All the three taxa elaborate mainly isoflavones (33 reported), occurring in the flowers, seeds/seed pods, stem bark and root bark. Out of the 33 isoflavones reported, some 19 (ca. 58%) contain prenyl at C-8 or its modification as 2,2-dimethylchromene ring at C-7/C-8, occurring in all the three taxa. Except for three isoflavones isolated from M. ferruginea subsp. darassana, all the isoflavones of these taxa are 5-deoxygenated. In these taxa, oxygenation at C-6 is a common feature, while isoflavones with C-8 oxygenation are rare, only three reported, and all of these from M. dura. There are 7 rotenoids reported from these taxa, and occur almost entirely in the seeds/seedpods of these plants. The major rotenoid with methylenedioxy group at C-2/C-3, millettone and its 12a-hydroxy derivative, millettosine, occur only in M. dura, this appears to distinguish M. dura from M. ferruginea.

Derese, S.  2020.  Synergistic anti-inflammatory activities of a new flavone and other flavonoids from Tephrosia hildebrandtii vatke. Natural Products Research. AbstractWebsite

Synergistic anti-inflammatory activities of a new flavone and other flavonoids from Tephrosia hildebrandtii vatke
Owor, R. O., Bedane, K. G., Openda, Y. I., Zühlke, S., Derese, S., Ong’amo, G., Ndakala, A., & Spiteller, M.
Abstract
A new flavone, named hildeflavone (1) along with 7 other known flavonoids were isolated from the aerial parts of Tephrosia hildebrandtii Vatke. Their characterisation was based on NMR and MS data analysis. The anti-inflammatory properties of the crude extract, isolated compounds and combination of the compounds were investigated in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the isolated flavonoids at a concentration of 100 µM significantly reduced the production of interleukins (IL-1β, IL-2 and IL-6), interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α). It was also found that the combination of a flavone and flavanones exhibited remarkable synergistic anti-inflammatory effects on the production of the cytokines.

Derese, S.  2020.  Anti-inflammatory Flavanones and Flavones from Tephrosia linearis. Journal of natural products. AbstractWebsite

Anti-inflammatory Flavanones and Flavones from Tephrosia linearis
Richard Oriko Owor, Kibrom Gebreheiwot Bedane, Sebastian Zühlke, Solomon Derese, George Otieno Ong’amo, Albert Ndakala, Michael Spiteller
Abstract
Phytochemical analysis of a methanol–dichloromethane (1:1) extract of the aerial parts of Tephrosialinearis led to the isolation of 18 compounds. Seven of these, namely, lineaflavones A–D (1–4), 6-methoxygeraldone (5), 8″-acetylobovatin (6), and 5-hydroxy-7-methoxysaniculamin A (7) are new compounds. The compounds were characterized based on their NMR and HRMSn data. The anti-inflammatory effects of the crude extract and isolated compounds were evaluated by measuring the levels of interleukins (IL-1β, IL-2, and IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). The crude extract inhibited the release of all cytokines except IL-1β, which slightly increased in comparison to the LPS control. All the tested compounds suppressed the production of IL-2, GM-CSF, and TNF-α. Whereas compounds 1, 2, 4–8, 10–15, 17, and 18 decreased production of IL-6, compounds 1, 2, 4, 7, 10, 13–15, and 17 inhibited the release of IL-1β. It is worth noting that most of the compounds tested showed a superior reduction in cytokines release compared to the reference drug ibuprofen.

Derese, S.  2020.  Two new flavonoids from Dracaena usambarensis Engl.. Phytochemistry Letters. 36:80-85. AbstractWebsite

Two new flavonoids from Dracaena usambarensis Engl.
Vaderament-A.Nchiozem-Ngnitedem, Leonidah Kerubo Omosa, Solomon Derese, PierreTane, Matthias Heydenreich, Michael Spiteller, Ean-Jeong Seo, Thomas Efferth

Investigations of the root extract of Dracaena usambarensis Engl. for anticancer principles led to the characterization of one new homoisoflavonoid, (3S)-3,4ʹ,5,6-tetrahydroxy-7-methoxyhomoisoflavanone (1) and a new retrodihydrochalcone, 4ʹ,4-dihydroxy-2,3-dimethoxydihydrochalcone (2) along with six previously reported compounds, including two homoisoflavonoids, 7-O-methyl-8-demethoxy-3-hydroxy-3,9-dihydropunctatin (3) and loureiriol (4); a phenolic amide, 3-(4ʹʹʹ-hydroxyphenyl)-N-[2ʹ-(4ʹʹ-hydroxyphenyl)-2ʹ-methoxyethyl]acrylamide (5); a spirostane, 25S-spirosta-1,4-dien-3-one (6) and two steroids, stigmasterol (7) and stigmasterol 3-O-β-D-glucopyranoside (8). The structures of 1-8 were determined using spectroscopic and spectrometric techniques. The absolute configurations of compounds 1 and 3 were achieved using circular dichroism spectroscopy. Using the resazurin reduction assay and doxorubicin as reference anticancer drug, 1 showed moderate cytotoxicity against drug sensitive CCRF-CEM but was inactive against all the other tested drug sensitive, resistance phenotypes and normal cells. The crude extract and 2-8 were inactive in the preliminary screening against CCRF-CEM and drug resistant CEM/ADR5000 cell lines. Interestingly, the activity of the standard drug, doxorubicin was comparable to those of inactive compounds against CEM/ADR5000 cells. Future studies should focus on structure modifications of 1-3, in order to obtain more potent analogues.

2019

Kyomuhimbo, HD.  2019.  Green Synthesis, Characterization And Antimicrobial Evaluation Of Silver And Zinc Oxide Nanoparticles From Extracts Of Bidens Pilosa. , Nairobi: University of Nairobi Abstract

There has been rampant outbreak of infectious diseases and various antibiotics have been introduced to treat these infections; however, they are turning out to be less effective due to their abuse leading to emergence of antimicrobial resistant infections. Various antiseptics have been used but their active ingredients are becoming ineffective to most resistant strains of bacteria. However, nanotization of antimicrobial agents has shown improvement of their disinfecting efficacy since nanoparticles have proved to have effective antimicrobial activity, even to resistant strains of microbes. In this study, nanotization of chemical constituents of Bidens pilosa was carried out because traditionally this plant is proven to have antimicrobial activity. In this study, biosynthesis of silver nanoparticles (AgNPs), zinc oxide-silver nanoparticles (ZnO-AgNPs) and zinc oxide nanoparticles (ZnONPs) using the seed, leaf and root extracts of Bidens pilosa with Silver nitrate and Zinc nitrate solutions, is reported. Extracts of Bidens pilosa contain a variety of bio-molecules such as polyphenols and water soluble heterocyclic compounds which reduce metal ions and stabilize nanoparticles. The plant (Bidens pilosa) was harvested; its seeds, leaves and roots were plucked, washed, dried under shed and crushed. The powders were dissolved in water to form extracts. The extracts were used to make AgNPs, ZnONPs and ZnO-AgNPs. The nanoparticles were characterized using UV-Vis spectroscopy, Fourier Transform Infrared, Raman spectroscopy, Scanning Electron Microscopy, Transmission Electron Microscopy, X-ray Diffraction and Atomic Force Microscopy. The antimicrobial activity of the nanoparticles was determined using agar well diffusion method. The most active nanoparticles were used as active ingredients in the formulation an antiseptic. The antimicrobial activity of the antiseptic was determined. The UV-Visible spectra showed a complete reduction of Ag+ ions to Ag0 with Plasmon resonance bands at around 410nm which is characteristic of AgNPs and formation of ZnONPs with a Plasmon resonance bands around 370nm. The synthesized nanoparticles had an average size of 2-20nm and were sphere-shaped without significant agglomeration as revealed from the SEM and TEM analysis. The synthesized AgNPs, ZnONPs and ZnO-AgNPs exhibited face–centered cubic crystals as demonstrated from XRD studies. FT-IR and Raman spectra of the seed, leaf and root extracts of Bidens pilosa, AgNPs, ZnONPs and ZnO-AgNPs revealed presence of vii functional groups C-O, O-H, =C–H, aromatic C-H bending, O-H, C=O, C=C aromatic and thiol groups attached to them. This indicated that these functional groups capped and stabilized the nanoparticles. Anti-Microbial activity of synthesized AgNPs, ZnONPs and ZnO-AgNPs against Escherichia coli, Staphylococcus aureus and a fungus Candida albicans were studied. Clear zones of inhibition were observed for the nanoparticles against the microorganisms. The ZnO-AgNPs obtained from the root extract of composition 0.8 Ag/0.2 ZnO had the highest antimicrobial activity. The ZnO-AgNPs obtained using root extracts of composition 0.8 Ag/0.2 ZnO were found to be effective as an active ingredient to make a hand sanitizing antiseptic against E. coli, and S. aureus bacteria and the fungus C. albicans.

Derese, S.  2019.  Silver–zinc oxide nanocomposite antiseptic from the extract of Bidens pilosa. Springer Nature Switzerland AG 2019. 1(7):681. Abstractsilver-zinc_oxide_nanocomposite_antiseptic_from_the_extract_of_bidens.pdf

Silver nanoparticles (Ag-NPs), zinc oxide (ZnO-NPs) and zinc oxide–silver (ZnO–Ag-NPs) were biosynthesized based on
the rich matrix of alkaloids, flavones, tannins capping/stabilizing agents present in Bidens pilosa extract. Different plant
parts-root, leaf and seed ware used to prepare the plant extract for synthesis. Also, zinc and silver nitrate salts were
used as precursor materials. The surface plasmon peaks (SPR) based on the UV–Vis results for the Ag-NPs, ZnO-NPs were
located between 408–411 and 365–450 nm respectively. The SPR peaks for the Ag–ZnO-NPs occurred at 300–450 nm
indicating both blue and red shifts. The Ag–ZnO-NPs SPR shifts were associated with possible nanoparticle size reduction
and change in dielectric constant of the synthesis medium. Raman measurement peaks at 356, 484, 1350, 1578,
2435 cm−1 associated with OH, –C==C–, –C–O, S=O, =C–H moieties indicated successful capping. Nanoparticle yield was
temperature dependent and optimal yield could not be tied to a particular plant part as source of extract. Tunneling
electron microscope results showed Ag-NPs and ZnO-NPs were globular/spherical with a diameter range of 2–20 nm.
Interestingly, ZnO-NPs TEM displayed isolated miniaturized globular nanoparticles (< 2 nm) which then joined up to form
a large donut shaped structure indicating different formation mechanisms for the nanoparticles. XRD results showed the
Ag-NPs, ZnO-NPs and the Ag–ZnO-NPs particles were crystalline in nature. The high signal/noise in XRD originated from
possible crystalline biomaterials in the extracts. Energy dispersive spectroscopy (EDS) elemental composition results
confirmed successful formation of the nanoparticles. Anti-Microbial activity of the synthesized Ag-NPs, ZnO-NPs and
ZnO–Ag-NPs were studied against gram negative bacteria Escherichia coli (E. coli), gram positive bacteria Staphylococcus
aureus and fungus Candida albicans. Different ZnO: Ag-NPs nanocomposite ratios were used to test for antimicrobial
activity. Optimal antimicrobial activity was attained at Ag-NPs:ZnO-NPs ratio of 4:1 which also displayed the least minimum
inhibition concentration (MIC) and therefore was used as the active ingredient in formulating a hand sanitizing
antiseptic. The formulated antiseptic exhibited good antimicrobial activity.
Keywords

2018

Derese, S.  2018.  Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity. Pharmaceutics. 10(4):232. Abstract

β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly (lactide-co-glycolic acid)(PLGA) and block copolymers of poly (ethylene glycol)-block-poly (lactic acid)(PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0±29.7 and 240.6±23.3 nm, a zeta potential of− 13.8±1.61 and− 23.5±0.27 mV, respectively, and with narrow size distribution. The encapsulation efficiency of β-Sit was 62.89±4.66 and 51.83±19.72% in PLGA and PEG-PLA nanoparticles, respectively. In vitro release in phosphate-buffered saline (PBS) and PBS/with 0.2% Tween 20 showed an initial burst release, followed by a sustained release for 408 h. β-Sit-PLGA nanoparticles were generally stable in a protein-rich medium, whereas β-Sit-PEG-PLA nanoparticles showed a tendency to aggregate. Flow cytometry analysis (FACS) indicated that β-Sit-PLGA nanoparticles were efficiently taken up by the cells in contrast to β …

Derese, S.  2018.  Crystal Structures and Cytotoxicity of ent-Kaurane-Type Diterpenoids from Two Aspilia Species. Molecules 23. 23(12):3199. Abstract

A phytochemical investigation of the roots of Aspilia pluriseta led to the isolation of ent-kaurane-type diterpenoids and additional phytochemicals (1–23). The structures of the isolated compounds were elucidated based on Nuclear Magnetic Resonance (NMR) spectroscopic and mass spectrometric analyses. The absolute configurations of seven of the ent-kaurane-type diterpenoids (3–6, 6b, 7 and 8) were determined by single crystal X-ray diffraction studies. Eleven of the compounds were also isolated from the roots and the aerial parts of Aspilia mossambicensis. The literature NMR assignments for compounds 1 and 5 were revised. In a cytotoxicity assay, 12α-methoxy-ent-kaur-9 (11), 16-dien-19-oic acid (1)(IC 50= 27.3±1.9 µM) and 9β-hydroxy-15α-angeloyloxy-ent-kaur-16-en-19-oic acid (3)(IC 50= 24.7±2.8 µM) were the most cytotoxic against the hepatocellular carcinoma (Hep-G2) cell line, while 15α-angeloyloxy-16β, 17-epoxy-ent-kauran-19-oic acid (5)(IC 50= 30.7±1.7 µM) was the most cytotoxic against adenocarcinomic human alveolar basal epithelial (A549) cells.

Derese, S.  2018.  Antiplasmodial prenylated flavanonols from Tephrosia subtrifloran . Natural product research. 32(12):1407-1414. Abstract

The CH2Cl2/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodium falciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC50 values 1.4–4.6 μM without significant cytotoxicity against Vero and HEp2 cell lines (IC50 > 100 μM). The new compound (1) showed weak antiplasmodial activity, IC50 12.5–24.2 μM, but also showed selective anticancer activity against HEp2 cell line …

Derese, S.  2018.  Modeling and synthesis of antiplasmodial chromones, chromanones and chalcones based on natural products of Kenya. Biofarmasi Journal of Natural Product Biochemistry. 16(1):8-21. Abstract

Scolastica M, Ndakala AJ, Derese S. 2018. Modeling and synthesis of antiplasmodial chromones, chromanones and chalcones based on natural products of Kenya. Biofarmasi J Nat Prod Biochem 16: 8-21. Despite numerous research that has been done on plants of Kenya resulting in the isolation of thousands of natural products, data on these natural products are not systematically organized in a readily accessible form. This has urged the construction of a web-based database of natural products of Kenya. The database is named Mitishamba and is hosted at http://mitishamba. uonbi. ac. ke. The Mitishamba database was queried for chromones, chromanones, and chalcones that were subjected to structure-based drug design using Fred (OpenEye) docking utility program with 1TV5 PDB structure of the PfDHODH receptor to identify complex of ligands that bind with the active site. Ligand-based drug design (Shape and electrostatics comparison) was also done on the ligands against query A77 1726 (38)(the ligand that co-crystallized with PfDHODH receptor) using ROCS and EON programs, respectively, of OpenEye suite. There was a substantial similarity among the top performing ligands in the docking studies with shape and electrostatic comparison that led to the identification of compounds of interest which were targeted for synthesis and antiplasmodial assay. In this study, a chromanone (7-hydroxy-2-(4-methoxyphenyl) chroman-4-one (48)) and two intermediate chalcones (2', 4'-dihydroxy-4-methoxychalcone (45) and 2’, 4’-dihydroxy-4-chlorochalcone (47)), were synthesized and subjected to antiplasmodial assay. Among these …

Derese, S.  2018.  Alkenyl cyclohexanone derivatives from Lannea rivae and Lannea schweinfurthii. Phytochemistry Letters. 23:141–148. Abstractalkenyl_cyclohexanone_derivatives_from_lannea_rivae_and_lannea.pdfWebsite

Phytochemical investigation of the CH2Cl2/MeOH (1:1) extract of the roots of Lannea rivae (Chiov) Sacleux (Anacardiaceae) led to the isolation of a new alkenyl cyclohexenone derivative: (4R,6S)-4,6-dihydroxy-6-((Z)-nonadec-14′-en-1-yl)cyclohex-2-en-1-one (1), and a new alkenyl cyclohexanol derivative: (2S*,4R*,5S*)-2,4,5-trihydroxy-2-((Z)-nonadec-14′-en-1-yl)cyclohexanone (2) along with four known compounds, namely epicatechin gallate, taraxerol, taraxerone and β-sitosterol; while the stem bark afforded two known compounds, daucosterol and lupeol. Similar investigation of the roots of Lannea schweinfurthii (Engl.) Engl. led to the isolation of four known compounds: 3-((E)-nonadec-16′-enyl)phenol, 1-((E)-heptadec-14′-enyl)cyclohex-4-ene-1,3-diol, catechin, and 1-((E)-pentadec-12′-enyl)cyclohex-4-ene-1,3-diol. The structures of the isolated compounds were determined by NMR spectroscopy and mass spectrometry. The absolute configuration of compound 1 was established by quantum chemical ECD calculations. In an antibacterial activity assay using the microbroth kinetic method, compound 1 showed moderate activity against Escherichia coli while compound 2 exhibited moderate activity against Staphylococcus aureus. Compound 1 also showed moderate activity against E. coli using the disc diffusion method. The roots extract of L. rivae was notably cytotoxic against both the DU-145 prostate cancer cell line and the Vero mammalian cell line (CC50 = 5.24 and 5.20 μg/mL, respectively). Compound 1 was also strongly cytotoxic against the DU-145 cell line (CC50 = 0.55 μg/mL) but showed no observable cytotoxicity (CC50 > 100 μg/mL) against the Vero cell line. The roots extract of L. rivae and L. schweinfurthii, epicatechin gallate as well as compound 1 exhibited inhibition of carageenan-induced inflammation.

2017

  2017.  Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp. teitensis. Journal of natural products. 80(7):2060-2066. AbstractWebsite

A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A–D (2–5), along with nine known compounds (6–14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 μM, respectively.

Derese, S.  2017.  Antiplasmodial prenylated flavanonols from Tephrosia subtriflora. Natural Product Research. 2017:1-8. AbstractWebsite

The CH2Cl2/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodium falciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC50 values 1.4–4.6 μM without significant cytotoxicity against Vero and HEp2 cell lines (IC50 > 100 μM). The new compound (1) showed weak antiplasmodial activity, IC50 12.5–24.2 μM, but also showed selective anticancer activity against HEp2 cell line (CC50 16.9 μM).

Derese, S.  2017.  Pterocarpans and isoflavones from the root bark of Millettia micans and of Millettia dura. Phytochemistry Letters . 21:216-220. Abstract

From the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia micans, a new pterocarpan, (6aR,11aR)-3-hydroxy-7,8,9-trimethoxypterocarpan (1), named micanspterocarpan, was isolated. Similar investigation of the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia dura gave a further new pterocarpan, (6aR,11aR)-8,9-methylenedioxy-3-prenyloxypterocarpan (2), named 3-O-prenylmaackiain, along with six known isoflavones (3-8) and a chalcone (9). All purified compounds were identified by NMR and MS, whereas the absolute configurations of the new pterocarpans were established by chriptical data analyses including quantum chemical ECD calculation. Among the isolated constituents, calopogonium isoflavone B (3) and isoerythrin A-4′-(3-methylbut-2-enyl) ether (4) showed marginal activities against the 3D7 and the Dd2 strains of Plasmodium falciparum (70–90% inhibition at 40 μM). Maximaisoflavone B (5) and 7,2′-dimethoxy-4′,5′-methylenedioxyisoflavone (7) were weakly cytotoxic (IC50 153.5 and 174.1 μM, respectively) against the MDA-MB-231 human breast cancer cell line. None of the tested compounds showed in-vitro translation inhibitory activity or toxicity against the HEK-293 human embryonic kidney cell line at 40 μM.

Muthaura, CN, Keriko JM, Mutai C, Yenesew A, Heydenreich M, Atilaw Y, Gathirwa JW, Irungu BN, Derese S.  2017.  Antiplasmodial, Cytotoxicity and Phytochemical Constituents of Four Maytenus Species Used in Traditional Medicine in Kenya. The Natural Products Journal. 7(2):144-152.
Derese, S, Guantai EM, Yaouba S, Kuete V.  2017.  Mangifera indica L. (Anacardiaceae). Medicinal Spices and Vegetables from Africa. , London: Elsevier Academic Press

2016

Rogo, MO.  2016.  Modeling and synthesis of antiplasmodial benzoxazines from natural products of Kenya. , Nairobi: University of Nairobi Abstract

Natural products research has taken place in Kenya for decades. This has led to the explosion of data about natural products which largely remains scattered in theses, published articles and books of abstracts and proceedings. As a result, natural products of Kenya are not accessible for drug design studies. Therefore the objective of this study was to create a webbased database of natural products of Kenya and use it in molecular modeling studies for the design of antiplasmodial compounds. Currently the database contains 1112 compounds. It has been named Mitishamba, a Kiswahili word referring to herbal medicine and is hosted online at (http://mitishamba.uonbi.ac.ke). The compounds in the database were utilized in the generation of suitable fragments for molecular modeling studies using the OpenyEye scientific software suite. Benzoxazine scaffold was identified as a suitable molecular framework, due to its similarity to Primaquine (an existing antimalarial drug). Analogs of the scaffold were generated and subjected to docking against the target, 3D shape comparison and electrostatics studies with promising molecules synthesized and assayed. A validated Plasmodium falciparum enzyme target, Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), was used in the docking studies. Three benzoxazines, 7- Methoxy-4H-1, 4-benzoxazin-3-one (25), (7-methoxy-3-oxo-1,4-benzoxazine-4- carbaldehyde (54) and 4-acetyl-7-methoxy-1,4-benzoxazin-3-one (56) were synthesized and then subjected to in vitro antiplasmodial assay against chloroquine resistant K1 and chloroquine sensitive 3D7 strains of P. falciparum. The results showed 7-methoxy-3-oxo- 1,4-benzoxazine-4-carbaldehyde had an activity of 11.05 μg/mL against chloroquine resistant K1 isolate while 4-acetyl-7-methoxy-1,4-benzoxazin-3-one had an activity of 8.32ug/mL. The latter has activity classified by the WHO as active and should be pursued further through optimization to investigate its antimalarial potency. The results above demonstrate the potential use of the database in the identification of lead antiplasmodial compounds. Therefore more benzoxazine derivatives should be identified through virtual screening and synthesized to optimize their antiplasmodial activity.

Omosa, LK, Midiwo JO, Mbaveng AT, Tankeo SB, Seukep JA, Voukeng IK, Dzotam JK, Isemeki J, Derese S, Omolle RA, Efferth T, Kuete V.  2016.  Antibacterial activities and structure–activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes. SpringerPlus. 5(1):1-15.
Marco, M, Deyou T, Gruhonjic A, Holleran JP, Duffy S, Heydenreich M, Fitzpatric PA, Landberg G, Koch A, Derese S, Pelletier J, Avery VM, Erdélyi Máté, Yenesew A.  2016.  Pterocarpans and Isoflavones from the Root Bark of Millettia micans and of Millettia dura. Advances in Drug Discovery and Development. :1-8. Abstract

Pterocarpans and Isoflavones from the Root Bark of Millettia micans and of
Millettia dura
Makungu Marco1, Tsegaye Deyou1,2, Amra Gruhonjic2,5, John P. Holleran3, Sandra Duffy3,
Matthias Heydenreich4, Paul A. Fitzpatrick5, Göran Landberg5, Andreas Koch4, Solomon
Derese1, Jerry Pelletier6, Vicky M. Avery3, Máté Erdélyi2,7,* and Abiy Yenesew1,*
1Department of Chemistry, University of Nairobi, P. O. Box 30197-00100, Nairobi, Kenya; 2Department of
Chemistry and Molecular Biology, University of Gothenburg, SE-40530, Gothenburg, Sweden; 3Discovery
Biology, Eskitis Institute for drug discovery, Griffith University, Nathan Qld 4111 Australia; 4Institut für Chemie,
Universität Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, Germany; 5Sahlgrenska Cancer
Centre, University of Gothenburg, SE-405 30 Gothenburg, Sweden; 6Department of Biochemistry, McGill
University, Montreal, QC, H3G 1Y6, Canada and 7Swedish NMR Center, University of Gothenburg, P.O. Box
465, SE-40530, Gothenburg, Sweden
Abstract: From the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia micans, a new pterocarpan,
(6aR,11aR)-7,8,9-trimethoxy-3-hydroxypterocarpan (1), named micanspterocarpan, was isolated. Similar
investigation of the CH2Cl2/CH3OH (1:1) extract of the root bark of Millettia dura gave a further new pterocarpan,
3-O-prenylmaackiain (2) along with six known isoflavones (3-8) and a chalcone (9). All purified
compounds were identified by NMR and MS, and the absolute configuration of 1 was established by quantum
chemical CD calculation. The isolated constituents, calopogonium isoflavone B (3) and isoerythrin A-4'-
(3-methylbut-2-enyl) ether (4) showed marginal activities against the 3D7 and the Dd2 strains of Plasmodium
falciparum (70-90% inhibition at 40

2015

Tsegaye, DW.  2015.  Phytochemical investigation of selected millettia (leguminosae) and ochna (ochnaceae) species for anticancer activities. , Nairobi: University of Nairobi Abstract

Despite the availability of well established cancer therapies, death from cancer is common and is predicted to rise. There is evidence that natural products play a significant role in cancer therapy and prevention; with considerable number of anticancer agents in use are either natural products or their derivatives. Flavonoids are among classes of natural products gaining a lot of interest as potential anticancer and cancer chemopreventive agents. In this regard, plants from two flavonoid rich genera, Millettia (Millettia oblata ssp. teitensis, Millettia dura and Millettia usaramensis ssp. usaramensis) of the Leguminosae family and Ochna (Ochna holstii and Ochna ovata) of the Ochnaceae family were investigated. Chromatographic (column chromatography on silica gel, Sephadex LH-20, preparative TLC and HPLC) separation of the extracts from the five plants led to the identification of a total of sixty six compounds, out of which ten are new. Four derivatives of the isolated compounds were also prepared. The structural elucidation of the compounds was performed using spectroscopic and spectrometric analyses: Nuclear Magnetic Resonance (NMR), Ultra Violet spectroscopy (UV), Circular Dichroism (CD), X-ray crystallography, Polarimetry and Mass Spectrometry (MS). The crude extract of the leaves of Millettia oblata ssp. teitensis yielded two new isoflavones (316 and 317) and four new structurally related rotenoids (318-321) along with eight known compounds. Similarly, the leaves of Millettia usaramensis ssp. usaramensis led to the identification of five rotenoids, three isoflavones and one triterpene, of which the isoflavone (312) is new. One of the known rotenoid (313) is reported here for the first time from the genus Millettia. The root bark extract of Millettia usaramensis ssp. usaramensis gave thirteen compounds (chalcones, rotenoids, flavanoids and cinnamyl alcohol) of which the chalcone (326) is a new compound. From the roots of Millettia oblata ssp. teitensis, thirteen compounds were identified. Among these, the tetraglycoside isoflavone (306) is a new compound. Similar work on the root bark of Millettia dura yielded six isoflavones, one chalcone and a pterocarpan, named 3-O-prenylmaakiain (303) is new compound. Similarly, investigation of the stem bark and leaves of Ochna holstii yielded dimeric and monomeric flavonoids along with dasycarponin (332) and 2,4-dihydroxyphenylmethyl acetate (335). Furthermore, the root bark of Ochna ovata also gave seven compounds some of which were also obtained from the stem and leaves of Ochna holstii. Four alkaloids (336-339) obtained from root bark of Ochna ovata are reported here for the first time from the family Ochnaceae. This is the first report on the phytochemistry of the two Ochna species. The crude extracts and some of their constituents were evaluated for anticancer activities. The crude extract of the roots of M. oblata ssp. teitensis showed strong activity (4.5 μg/mL) against ER-negative MDB-MB-231 human breast cancer cell-line followed by crude extract of root bark of M. usaramensis ssp usaramensis (11.6 μg/mL). The pure compounds were also found cytotoxic aganist ER-negative MDB-MB-231 human breast cancer cell-line (IC50 10.5-88.1 μg/mL) among which the highest activity was recorded for usararotenoid C (154, 10.5 μg/mL) followed by maximaisoflavone J (325, 11.2 μg/mL). The activity of 154 is almost four times higher than that of epimillettosin (137, 39.7 μg/mL) with the only structural difference between the two is that 154 has a prenyl group at C-8 and a methoxyl group at C-9 while in 137 the prenyl has cyclized into 2,2-dimethylchromene. Similarly, the activity of maximaisoflavone J (325) is almost five times higher than maximaisoflavone B (304, 53.8 vii μg/mL); while the only difference between the two compounds is the replacement of the methoxyl group at C-4' in 325 by a methylenedioxy (C-3'/C-4') in maximaisoflavone B (304). The strong activities observed for the crude extracts; roots of Millettia oblata ssp. teitensis and root bark of Millettia usaramensis ssp. usaramensis could be due to their active component; maximaisoflavone J (325) and usararotenoid C (154), respectively. Some compounds were also evaluated for cytotoxicity against Vero cells (IC50 6.7-67.4 μg/mL). Strong activity was recorded for the dimeric flavonoid, calodenone (253). This compound is ten times more active than the related compound, lophirone A (252), a compound which only differ from 253 by lack of a methoxyl group at C-15. The isolated constituents were also tested in Krebs-2 in vitro for translation inhibitory, but none of the compounds showed translation inhibitory activity. Overall, the investigation of the five plants yielded a wide range of new and known compounds as monomeric and dimeric flavonoids, rotenoids, isoflavonoids, chalcones, alkaloids, triterpene and two simple molecules (331 and 335), some of which showed moderate to low cytotoxicity on the ER-negative MDB-MB-231 human breast cancer cell-line and Vero cells.....

Chege, IN, Okalebo FA, Guantai AN, Karanja S, Derese S.  2015.  The Effects of Selected Kenyan Herbal Formulations on Glucose, Lipid Levels and Hepatic Function in Alloxan Induced Diabetic Rats. Global journal of Biotechnology, Agriculture & Health Sciences. 4(2):101-107. AbstractUSIU Digital Repository

Abstract
Introduction: Polyherbal formulations used for management of diabetes in Kenya lack studies to determine their
efficacy or safety. Objective: To evaluate the efficacy and safety of two anti-diabetic polyherbal formulations (LUC and
MUI). Method: Herbs were collected, dried and formulated. Formulations were evaluated using grouped alloxan induced
wistar rats. Effects were compared to conventional drugs; pioglitazone (3mg/kg bw), glibenclamide (100 mg/kg bw),
metformin (100 mg/kg bw) and normal control group. Each group received an individual drug/water once daily orally for
fourteen days. Blood glucose levels were evaluated every seven days using a glucometer. Liver function tests and lipid
profile were measured on day 14. The data was expressed in mean ± SEM. Analysis was by ANOVA and post hoc multicomparison Turkey test (p < 0.05). Results: No mortalities reported. Both herbal preparations had hypoglycemic effects.
LUC was more potent. MUI increased all lipid levels. LUC caused intestinal gas distention on gross examination.
Conclusion: The herbal formulations were hypoglycemic at the tested doses.
Key words: polyherbal formulations, diabetes mellitus

Derese, S.  2015.  Seed, Foster, Believe, Dream and Act. Capacity Building in Kenya by Novartis Global Discovery Chemistry, Seeding Labs, the International Activities Committee, and the Computers in Chemistry Division of the ACS between 2010−2014. ACS Symposium Series Vol 1195. : Amercian Chemical Society Abstract

Novartis initiated a Fellows program for African academic scientists in 2010 in partnership with Seeding Labs, providing a 9 week-long industrial immersion experience at the Novartis Institutes for Biomedical Research (NIBR) in Cambridge Massachusetts. Through their scientific projects and activities, the Fellows explored new laboratory techniques and improved their scientific communication and grant writing skills. A primary aim of the program was to influence the Fellows’ time in the NIBR laboratories into promoting research of potential utility to their scientific and teaching activities on returning home to their academic institutions, thus building strength in scientific capacity in Africa. As chemistry is an essential discipline in the drug-discovery process, it has been an area of focus for several visiting African Fellows and their NIBR scientific mentors. In particular, computational chemistry has minimal laboratory requirements and is ideally suited as an area for scientific capacity building in Africa. In addition, extending drug-discovery capabilities in African laboratories to assist natural products research is of interest, particularly concerning development of treatments for malaria, tuberculosis, HIV and, of recent concern, the West African Ebola outbreak. An ACS International Activities Committee Global Innovation Grant, granted in 2012 added financial momentum to this capacity building project, spurring our efforts in capturing a Canadian Grand Challenges award and the pursuit of funding from IUPAC. In 2014, this initiative reached two significant milestones, creation of its first job, a computational chemistry academic faculty position in Kenya, and the launch of an in-silico database of Kenyan natural products named Mitishamba.

IN Chege, Okalebo FA, A Nkatha Guantai, S Karanja, Derese S.  2015.  Management of type 2 diabetes mellitus by traditional medicine practitioners in Kenya-key informant interviews. The Pan African Medical Journa. 22(90):1-12. Abstract

Abstract
Introduction: worldwide, plant based medicines are increasing in popularity due to perceptions of safety and efficacy. Herbalists in Kenya are widely consulted for the management of many diseases including Type 2 Diabetes Mellitus (T2DM). This study investigated the level of knowledge of the herbalists in management of T2DM.

Methods: purposive sampling was used to identify 4 herbalists working in the urban areas who actively manage T2DM. Key informant interviews were used to gather data about the management of T2DM. It was analyzed using a content thematic approach.

Results: diverse management methods which included both pharmacological and non- pharmacological were noted. Glycemic control was assessed with the help of a glucometer. In addition, presenting signs and symptoms were key in diagnosing T2DM. The herbalists used various herbs, minerals and animals as medicinal sources. The drugs were dispensed as decoctions with excipients being added appropriately. Adverse effects were recorded. The herbalists acknowledged that patients use both herbal and allopathic medicine together. A level of record keeping was observed but patient follow-up was poor. The cost of the herbal drugs was perceived to be excessive.

Conclusion: some similarities exist in the management of T2DM between allopathic and traditional medicine practitioners. Training of herbalists is required to improve the quality of care given to patients.

CN, M, Keriko JM, Mutai C, A Y, Gathirwa JW, Irungu BN, Nyangacha R, Mungai GM, s. D.  2015.  Antiplasmodial potential of traditional phytotherapy of some remedies used in treatment of malaria in Meru-Tharaka Nithi County of Kenya. J Ethnopharmacol.. 175(3):15-23. Abstract

J Ethnopharmacol. 2015 Dec 4;175:315-23. doi: 10.1016/j.jep.2015.09.017. Epub 2015 Sep 25.
Antiplasmodial potential of traditional phytotherapy of some remedies used in treatment of malaria in Meru-Tharaka Nithi County of Kenya.
Muthaura CN1, Keriko JM2, Mutai C3, Yenesew A4, Gathirwa JW5, Irungu BN5, Nyangacha R5, Mungai GM6, Derese S4.
Author information
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE:
Medicinal plants play a major role in many communities across the world, in the treatment and prevention of disease and the promotion of general health. The aim of the study was to escalate documentation from an earlier study of medicinal plants, traditionally used to combat malaria by the Ameru community of Imenti Forest area and Gatunga in Eastern Region of Kenya, and validate their ethnopharmacological claims by evaluating their antiplasmodial efficacies.
MATERIALS AND METHODS:
The study was carried out in Meru County at Imenti Forest Game Reserve and in Tharaka Nithi County at Gatunga. Traditional health practitioners (THP) were interviewed with a standard questionnaire to obtain information on medicinal plants traditionally used for management of malaria. Group interviews were also held among THPs and members of the community. The antiplasmodial activities of the crude extracts against chloroquine sensitive (D6) and resistant (W2) Plasmodium falciparum were determined using the semi-automated micro-dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-3H) hypoxanthine into the malaria parasite.
RESULTS:
Ninety nine (99) species in eighty one (81) genera and forty five (45) families were documented and evaluated for in vitro antiplasmodial activity. Compositae, Fabaceae, Meliceae, Rubiaceae, Rutaceae and Verbenaceae had the highest number of species mentioned in treatment of malaria in Meru/Tharaka Nithi study area. Twenty four (24.2%) species showed antiplasmodial efficacy of IC50≤5µg/ml and were considered to have potential for isolation of antimalarial compounds. Eight plant (8) species with moderate antiplasmodial activity namely; Cordia africana, Commiphora africana, Elaeodendron buchananii, Gomphocarpus semilunatus, Tarena graveolens, Plectranthus igniarius, Acacia senegal and Ziziphus abyssinica were documented from this region for the first time for the treatment of malaria. The antiplasmodial activity of MeOH root bark extract of Maytenus obtusifolia was very promising (IC50<1.9µg/ml) and this is the first report on traditional use of M. obtusifolia for treatment of malaria and antimalarial activity.
CONCLUSIONS:
The results seem to indicate that ethnopharmacological inquiry used in search for new herbal remedies as predictive and could be used as the basis for search of new active principles. Eight plant (8) species are documented from this region for the first time for the treatment of malaria. This is the first report on traditional use of M. obtusifolia for treatment of malaria and evaluation of its antiplasmodial activity.

T, D, I G, F P, A G, Mumo M, Holleran J, Duffy S, Fitzpatrick PA, Heydenreich M, G L, S D, Avery V, Rissanen K, Erdélyi M, A Y.  2015.  Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis.. J Nat Prod. 78(12):2932-9. Abstract

J Nat Prod. 2015 Dec 24;78(12):2932-9. doi: 10.1021/acs.jnatprod.5b00581. Epub 2015 Dec 14.
Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis.
Deyou T1, Gumula I1, Pang F2, Gruhonjic A, Mumo M1, Holleran J3, Duffy S3, Fitzpatrick PA, Heydenreich M4, Landberg G, Derese S1, Avery V3, Rissanen K2, Erdélyi M, Yenesew A1.
Author information
Abstract
Five new compounds, 4-O-geranylisoliquiritigenin (1), 12-dihydrousararotenoid B (2), 12-dihydrousararotenoid C (3), 4'-O-geranyl-7-hydroxyflavanone (4), and 4'-O-geranyl-7-hydroxydihydroflavanol (5), along with 12 known natural products (6-17) were isolated from the CH2Cl2/MeOH (1:1) extract of the root bark of Millettia usaramensis ssp. usaramensis by chromatographic separation. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas their absolute configurations were established on the basis of chiroptical data and in some cases also by X-ray crystallography. The crude extract was moderately active (IC50 = 11.63 μg/mL) against the ER-negative MDB-MB-231 human breast cancer cell line, and accordingly compounds 6, 8, 9, 10, 12, and 16 also showed moderate to low cytotoxic activities (IC50 25.7-207.2 μM). The new natural product 1 exhibited antiplasmodial activity with IC50 values of 3.7 and 5.3 μM against the chloroquine-sensitive 3D7 and the chloroquine-resistant Dd2 Plasmodium falciparum strains, respectively, and was also cytotoxic to the HEK293 cell line.

Irene Njeri Chege, Faith Apolot Okalebo, ANGSKSD.  2015.  Herbal Product Processing Practices of Traditional Medicine Practitioners in Kenya-Key Informant Interviews. Journal of Health, Medicine and Nursing. 16:11-23. Abstract24799-27406-1-pb_1.pdf

Herbal Product Processing Practices of Traditional Medicine Practitioners in Kenya-Key Informant Interviews
Irene Njeri Chege, Faith Apolot Okalebo, Anastasia Nkatha Guantai, Simon Karanja, Solomon Derese
Journal of Health, Medicine and Nursing, 2015, 16, 11-23

Abstract
Introduction: Herbalists in Kenya use self-taught processing practices which are inadequate. The objective of
this study was to conduct an assessment of selected practices used by herbalists during drug processing and to
identify knowledge gaps.
Method: Four long practicing traditional medicinal practitioners were identified using purposive sampling. An
interview guide and field visits were used to gather data. Data analysis was done using content thematic
approach.
Results: Sources of herbal knowledge were varied with the use of internet being a key finding. Regulatory
compliance presented various challenges to the herbalists. The wild and cultivation of herbs were identified as
key medicinal sources although the protection of biodiversity was a key concern of the herbalists. The facilities,
area of practice and general hygiene were inadequate. Positive and negative practices were identified in
processing of the herbal medicines.
Conclusions: Secrecy by the herbalists has resulted in limited in innovation. More training of herbalists is
required to improve on the quality of their drugs. It is however encouraging that they have adopted some
modern methods in their practice.
Keywords: Herbalists, processing practices, herbal drugs

Muthaura CN, Keriko JM, MYGJWIBNNMGMDCAR.  2015.  Antiplasmodial potential of traditional antimalarial phytotherapy remedies used by the Kwale community of the Kenyan coast. Journal of ethnopharmacology. 170:148-157. Abstract

Antiplasmodial potential of traditional antimalarial phytotherapy remedies used by the Kwale community of the Kenyan Coast.

Muthaura CN, Keriko JM, Mutai C, Yenesew A, Gathirwa JW, Irungu BN, Nyangacha R, Mungai GM, Derese S
Kenya Medical Research Institute, P.O. Box 54840, 00200 Nairobi, Kenya. Electronic address: cmuthaura@yahoo.com.
Journal of Ethnopharmacology [2015, 170:148-157]

ETHNOPHARMACOLOGICAL RELEVANCE: In Kenya, 22 million people are at risk of malaria, 70% of them are in rural areas and most of these people use traditional plant based medicines to treat malaria. The aim of the study was to escalate documentation, from an earlier study of medicinal plants, traditionally used to treat malaria by the Digo community of Kwale County, taking cognizance of their pharmacological information by evaluating their antiplasmodial efficacies.

MATERIALS AND METHODS: The study was carried out in Kwale County at Shimba Hills Game Reserve and adjoining part of Kinango. Traditional health practitioners (THP) were interviewed with a standard questionnaire to obtain information on medicinal plants traditionally used for management of malaria. Group interviews were also held among THPs and members of the community. The plant samples collected were tested for antiplasmodial activity against chloroquine sensitive (D6) and resistant (W2) Plasmodium falciparum using the ability of extracts, prepared from the plant species, to inhibit the incorporation of [G-3H] hypoxanthine into the malaria parasites.

RESULTS: Fifty seven (57) species in forty eight (48) genera and thirty (30) families were documented and evaluated for in vitro antiplasmodial activity. Apocynaceae, Euphorbiaceae, and Rubiaceae families had each about 12% of the plant species reported as antimalarial remedy and represented the species that are most commonly used. Twelve species (21.1%) showed antiplasmodial efficacy of IC50<5µg/ml and these were Boscia salicifolia, Cissampelos mucronata, Clerodendrum myricoides, Commiphora schimperi, Flueggea virosa, Maytenus undata, Maytenus senegalensis, Maytenus putterlickioides, Vernonia amygdalina, Warburgia stuhlmannii, Zanthoxylum chalybeum and Tabernaemontana pachysiphon.

CONCLUSIONS: These results seem to indicate that ethnopharmacological inquiry used in search for new herbal remedies as predictive and could form the basis of an ethnopharmacopoeia and search for new active principles. This is the first report on traditional use of T. pachysiphon for malaria and its antiplasmodial activity.

2014

Lois Muiva-Mutisya, Bernard Macharia, MHAKHASDLOAMK.  2014.  6α-Hydroxy-α-toxicarol and (+)-tephrodin with antiplasmodial activities from Tephrosia species. Phytochemistry Letters. 10:179-183. Abstract

6α-Hydroxy-α-toxicarol and (+)-tephrodin with antiplasmodial activities from Tephrosia species

Lois Muiva-Mutisyaa, Bernard Machariaa, Matthias Heydenreichb, Andreas Kochb, Hoseah M. Akalac, Solomon Deresea, Leonidah K. Omosaa, Amir O. Yusufa, Edwin Kamauc, Abiy Yenesew
Phytochemistry Letters, Volume 10, December 2014, Pages 179–183

Abstract
The CH2Cl2/MeOH (1:1) extract of the roots of Tephrosia villosa showed good antiplasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3.1 ± 0.4 and 1.3 ± 0.3 μg/mL, respectively. Chromatographic separation of the extract yielded a new rotenoid, 6α-hydroxy-α-toxicarol, along with five known rotenoids, (rotenone, deguelin, sumatrol, 12a-hydroxy-α-toxicarol and villosinol). Similar treatment of the extract of the stem of Tephrosia purpurea (IC50 = 4.1 ± 0.4 and 1.9 ± 0.2 μg/mL against D6 and W2 strains of P. falciparum, respectively) yielded a new flavone having a unique substituent at C-7/C-8 [trivial name (+)-tephrodin], along with the known flavonoids tachrosin, obovatin methyl ether and derrone. The relative configuration and the most stable conformation in (+)-tephrodin was determined by NMR and theoretical energy calculations. The rotenoids and flavones tested showed good to moderate antiplasmodial activities (IC50 = 9 − 23 μМ). Whereas the cytotoxicity of rotenoids is known, the flavones (+)-tephrodin and tachrosin did not show significant cytotoxicity (IC50 > 100 μМ) against mammalian African monkey kidney (vero) and human larynx carcinoma (HEp2) cell lines.

Derese, S.  2014.  4′-Prenyloxyderrone from the stem bark of Millettia oblata ssp. teitensis and the antiplasmodial activities of isoflavones from some Millettia species. Phytochemistry Letters. 8:69-72. Abstract

4′-Prenyloxyderrone from the stem bark of Millettia oblata ssp. teitensis and the antiplasmodial activities of isoflavones from some Millettia species

Solomon Derese, Leonard Barasa, Hoseah M. Akala, Amir O. Yusuf, Edwin Kamau, Matthias Heydenreich, Abiy Yenesew

The CH2Cl2/MeOH (1:1) extract of the stem bark of Millettia oblata ssp. teitensis showed antiplasmodial activity (IC50 = 10–12 μg/mL) against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Chromatographic separation of the extract led to the isolation of a new isoflavone, 4′-prenyloxyderrone (1), together with known isoflavones (8-O-methylretusin, durmillone, maximaisoflavone B, maximaisoflavone H and maximaisoflavone J), a rotenoid (tephrosin) and a triterpene (lupeol). Similar investigation of Millettia leucantha resulted in the identification of the isoflavones afrormosin and wistin, and the flavone chrysin. The identification of these compounds was based on their spectroscopic data. Five of the isoflavones isolated from these plants as well as 11 previously reported compounds from Millettia dura were tested and showed good to moderate antiplasmodial activities (IC50 = 13–53 μM), with the new compound, 4′-prenyloxyderrone, being the most active (IC50 = 13–15 μM).

2013

Derese, S.  2013.  Antiplasmodial activity of compounds from the surface exudates of Senecio roseiflorus. Natural product communications. 8(2):175-6. Abstract

Antiplasmodial activity of compounds from the surface exudates of Senecio roseiflorus.

Leonidah Omosa Kerubo, Jacob Ogweno Midiwo, Solomon Derese, Moses K Langat, Hosea M Akala, Norman C Waters, Martin Peter, Matthias
Natural Products Communications: 2013; 8(2):175-6.

From the surface exudates of Senecio roseiflorus fourteen known methylated flavonoids and one phenol were isolated and characterized. The structures of these compounds were determined on the basis of their spectroscopic analysis. The surface exudate and the flavonoids isolated showed moderate to good antiplasmodial activity with 5,4'-dihydroxy-7-dimethoxyflavanone having the highest activity against chloroquine-sensitive (D6) and resistant (W2) strains of Plasmodium falciparum, with IC50 values of 3.2 +/- 0.8 and 4.4 +/- 0.01 microg/mL respectively.

2012

Buyinza, D.  2012.  Phytochemical investigation of Zanthoxylum holstzianum for antimicrobial principles. , Nairobi: University of Nairobi Abstract

As a response to the worldwide alarm of increased resistance of microbes to readily available antibiotics, the stem bark of Zanthoxylum holstzianum (Rutaceae) with no prior phytochemical report was investigated so as to isolate, and elucidate secondary metabolites with likely antimicrobial activities. The plant material was collected from Diani Veminant forest (coastal province of Kenya), dried at room temperature under shade, pulverised and extracted using acetone. The crude extract was subjected to fractionation and purification using a range of separation techniques including, partitioning, Column Chromatography (CC), Preparative Thin Layer Chromatography (PTLC) and crystallization. The structure of the isolated compounds was determined using a combination of spectroscopic techniques such as UV, MS, and NMR.
In total seven compounds were isolated, of these, three were benzophenanthridine alkaloids dihydrochelerythrine (2), 8-acetonyldihydrochelerythrine (5) and 8oxochelerythrine (7)], one canthin-6-one alkaloid [N-methylflindersine (3)], a flavanone
[hesperidine (1)], a fatty acid [hexadecanoic acid (6)], and an amide (2E,4E)-Nisobutyltetradeca-2,4-dienamide (4)]. This is the first report of the occurrence of (2E,4E)N-isobutyltetradeca-2,4-dienamide (4), hexadecanoic acid (6) and hesperidin (1) from the genus Zanthoxylum. A summary of the isolated compounds is shown in figure 1. The crude extract and isolated compounds were screened against four microbial
pathogens, namely: Escherichia coli NC 35218 (Bacterium), Staphylococcus aureus
ATCC 259213 (Bacterium), Candida albicans SC 5314 (Yeast fungus), and Aspergillus
niger ATCC 16404 (Filamentous fungus) using the disc diffusion technique as
recommended by the Clinical and Laboratory Standards Institute (CLSI, 2012).
Dihydrochelerythrine (2), N-methylflindersine (3), (2E, 4E)-N-isobutyltetradeca-2,4dienamide (5) and the crude extract, each had minimum inhibition concentration (MIC)
of 6.25 μg/disc against Staphylococcus aureus. The crude had MIC of 62.5 μg/disc
against Candida albicans and the essential oils showed a MIC of 12.5 μg/disc against
both Staphylococcus aureus and Candida albicans.

SOLOMON, DRDERESE.  2012.  Four isoflavanones from the stem bark of Platycelphium voense. Phytochemistry Letters. 5(1):150–154.: Elsevier AbstractScienceDirect

From the stem bark of Platycelphium voënse (Leguminosae) four new isoflavanones were isolated and characterized as (S)-5,7-dihydroxy-2′,4′-dimethoxy-3′-(3″-methylbut-2″-enyl)-isoflavanone (trivial name platyisoflavanone A), (±)-5,7,2′-trihydroxy-4′-methoxy-3′-(3″-methylbut-2″-enyl)-isoflavanone (platyisoflavanone B), 5,7-dihydroxy-4′-methoxy-2″-(2‴-hydroxyisopropyl)-dihydrofurano-[4″,5″:3′,2′]-isoflavanone (platyisoflavanone C) and 5,7,2′,3″-tetrahydroxy-2″,2″-dimethyldihydropyrano-[5″,6″:3′,4′]-isoflavanone (platyisoflavanone D). In addition, the known isoflavanones, sophoraisoflavanone A and glyasperin F; the isoflavone, formononetin; two flavones, kumatakenin and isokaempferide; as well as two triterpenes, betulin and β-amyrin were identified. The structures were elucidated on the basis of spectroscopic evidence. Platyisoflavanone A showed antibacterial activity against Mycobacterium tuberculosis in the microplate alamar blue assay (MABA) with MIC = 23.7 μM, but also showed cytotoxicity (IC50 = 21.1 μM) in the vero cell test.

SOLOMON, DRDERESE.  2012.  Antiplasmodial Quinones from Pentas longiflora and Pentas lanceolata. Planta Medica. 78:31–35.: Thieme AbstractWebsite

Milkyas Endale, John Patrick Alao, Hoseah M. Akala, Nelson K. Rono, Fredrick L. Eyase, Solomon Derese,
Albert Ndakala, Martin Mbugua, Douglas S.Walsh, Per Sunnerhagen, Mate Erdelyi, Abiy Yenesew

Planta Med 2012; 78: 31–35

The dichloromethane/methanol (1 :1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC50 = 0.9–3 μg/mL) in vitro antiplasmodial activity against chloroquineresistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. Chromatographic separation of the extract of Pentas longiflora led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC50 values below 1 μg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones (4–11, IC50 = 5–31 μg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three – nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10) – are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.

2011

Yenesew, A, Gumuia I, Heydenreich M, Derese S, Okalebo FA, Ndiege IO, Erdelyi M.  2011.  Bioactivity of 'Flemingin A' and other Natural Products from the leaves of Flemingia grahamiana. yenesew.pdfWebsite
SOLOMON, DRDERESE.  2011.  Investigation of some medicinal plants traditionally used for treatment of malaria in Kenya as potential sources of antimalarial drugs.. Experimental Parasitology. 127(2):609–626.: Elsevier AbstractScienceDirect

Malaria is a major public health problem in many tropical and subtropical countries and the burden of this disease is getting worse, mainly due to the increasing resistance of Plasmodium falciparum against the widely available antimalarial drugs. There is an urgent need for discovery of new antimalarial agents. Herbal medicines for the treatment of various diseases including malaria are an important part of the cultural diversity and traditions of which Kenya′s biodiversity has been an integral part. Two major antimalarial drugs widely used today came originally from indigenous medical systems, that is quinine and artemisinin, from Peruvian and Chinese ancestral treatments, respectively. Thus ethnopharmacology is a very important resource in which new therapies may be discovered. The present review is an analysis of ethnopharmacological publications on antimalarial therapies from some Kenyan medicinal plants.

2010

SOLOMON, DRDERESE.  2010.  Antimicrobial and antiparasitic abietane diterpenoids from the roots of Clerodendrum eriophyllum.. Natural Products Communication. 5(6):853-858.: Elsevier AbstractWebsite

Machumi F, Samoylenko V, Yenesew A, Derese S, Midiwo JO, Wiggers FT, Jacob MR, Tekwani BL, Khan SI, Walker LA, Muhammad I.; Nat Prod Commun. 2010 5(6), pp. 853-8.

Chromatographic separation of the roots of a Kenyan medicinal plant, Clerodendrum eriophyllum, led to the isolation of ten abietane diterpenoids (1-10), one of which (1) was isolated for the first time from a natural source. Using spectroscopic data, the structure of 1 was determined to be 12-hydroxy-8,12-abietadiene-3,11,14-trione. Circular dichroism (CD) spectra showed that the stereochemistry of compounds 1, 3, and 6-8 belongs to the normal series of abietane diterpenes, which confirmed the absolute stereochemistry of the isolated compounds. Compounds 1-10 were evaluated for their in vitro antiplasmodial, antileishmanial, antifungal and antibacterial activities. Compounds 3 and 7 exhibited potent antifungal activity (IC50/MIC 0.58/1.25 and 0.96/2.5 microg/mL, respectively) against C. neoformans, whereas 3, 6 and 7 showed strong antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with IC50/MIC values between 1.33-1.75/2.5-5 and 0.96-1.56/2.5 microg/mL, respectively. In addition, compounds 3 and 9 exhibited potent antileishmanial activity (IC50 0.08 and 0.20 microg/mL, respectively) against L. donovani, while 3 and 7 displayed weak antimalarial activity against Plasmodium falciparum, but 9 was inactive.

SOLOMON, DRDERESE.  2010.  neo-Clerodane diterpenoids from the leaf exudate of Dodonaea angustifolia.. Phytochemistry Letters. 3(4):217-220.: Elsevier AbstractWebsite

Leonidah K. Omosa, Jacob O. Midiwo, Solomon Derese, Abiy Yenesew, Martin G. Peter, Matthias Heydenreich.

Phytochemical investigation of the leaf surface exudate of Dodonaea angustifolia L.f. yielded two new neo-clerodane diterpenes, neo-clerodan-3,13-dien-16,15:18,19-diolide (mkapwanin) and 15-methoxy-neo-clerodan-3,13-dien-16,15:18,19-diolide (15-methoxymkapwanin). In addition, ten known compounds were identified. The structures were determined on the basis of spectroscopic evidence. This additional chemical information could contribute towards solving the taxonomical controversy that exists between Dodonaea angustifolia and Dodonaea viscosa Jacq., which are morphologically similar.

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