Publications


In Press

2020

Omole, RA, Moshi MJ, Ilias M, Larry W, Malebo HM, Omosa LK, Midiwo JO.  2020.  In vitro Antiplasmodial and Cytotoxic activity of Three Medicinal Plants used Traditionally for Treatment of Malaria.. Pharmacognosy Communications. 10(1):2-6. AbstractPharmacognosy Communications

Description
Introduction:
Reports of emergence of Artemisinin Combination Therapies (ACTs) resistant malaria parasites in Greater Mekong region and Equatorial Guinea, is a strong reason necessitating increased efforts to discover new antimalarial compounds with novel mechanisms of action. Plants have potential to yield new antiplasmodial compounds. This study investigated the safety and efficacy of three plants; Bersama abyssinica Fresen, Rubus keniensis Standl and Hypoestes verticillaris (Lf) Sol. ex Roem. and Schult that are used by the Ogiek community of Kenya for treatment of malaria.
Methodology:
The crude extracts were tested for in vitro antimalarial activity using Plasmodium falciparum strains W2 (chloroquine resistant) and D6 (chloroquine sensitive). Safety evaluation was done using monkey kidney Vero cells and the brine shrimp lethality test.
Results:
Dichloromethane: methanol (1: 1) and 5% aqueous methanol extracts of the three plants exhibited in vitro antiplasmodial activity against the W2 and D6 Plasmodium falciparum strains with IC50= 12.11–19.18 µg/mL, 5.46-7.04 µg/mL and 9.82–34.52 µg/mL, respectively. H. verticillaris extracts were the most active against the two Plasmodium falciparum strains. The dichloromethane: methanol extracts of the three plants exhibited lower toxicity on monkey kidney Vero cells relative to antiplasmodial activity as compared to the 5% aqueous methanol extracts. The mean Vero cells: parasite selectivity index of the dichloromethane: methanol extracts was (4.8), B. abyssinica (3.75) and R. keniensis (1.9), while for the 5% aqueous methanol extracts they were H. verticillaris (1.0), B. abyssinica (1.95 …

2019

Kuete, V, Omosa LK, Midiwo JO, Karaosmanoğlu O, Sivas H.  2019.  Cytotoxicity of naturally occurring phenolics and terpenoids from Kenyan flora towards human carcinoma cells. Journal of Ayurveda and integrative medicine. 10(3):178-184. AbstractJournal article

Description
Background
Cancer constitutes a major hurdle worldwide and its treatment mainly relies on chemotherapy.
Objectives
The present study was designed to evaluate the cytotoxicity of eleven naturally occurring compounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normal CRL2120 fibroblasts.
Materials and methods
The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) was measured by spectrophotometry.
Results
Chalcones: 2′,4′-dihydroxy-6′-methoxychalcone (1); 4′,6′-dihydroxy-2′,5′-dimethoxychalcone (2); 2′,4 …
Scholar articles
Cytotoxicity of naturally occurring phenolics and terpenoids from Kenyan flora towards human carcinoma cells
V Kuete, LK Omosa, JO Midiwo, O Karaosmanoğlu… - Journal of Ayurveda and integrative medicine, 2019
Related articles All 3 versions

Omole, RA, Moshi MJ, Heydenreich M, Malebo HM, Gathirwa JW, Oriko RO, Omosa LK, Midiwo JO.  2019.  Antiplasmodial Biflavanones from the Stem Bark of Garcinia buchananii Engl.. Pharmacognosy Communications. 9(3):96-99. AbstractJournal article

Description
Introduction: Plants of the genus Garcinia are traditionally used treat a range of infectious and non-infectious diseases. Garcinia species are reported to have been shown to have a range of biological activities including cytotoxicity antimicrobial, antifungal, antioxidant, antimalarial and HIV-1 protease inhibitory activity among others. Methods: Solvent extraction was done using CH2Cl2: MeOH (1: 1). Isolation was done using column chromatography with silica gel as the stationery phase and ethyl acetate and n-hexane used as mobile phase in increasing polarity. Thin layer chromatography was used to monitor the isolation. Structure elucidation was done using nuclear magnetic resonance and mass spectroscopic techniques. Chloroquine resistant (W2) and chloroquine sensitive (D6) P. falciparum strains were used for antiplasmodial assay. Results: Further bioassay guided fractionation of a CH2Cl2: MeOH (1: 1) extract of Garcinia buchananii led to the isolation of two already reported biflavanones, isogarcinol (1) and guttiferone (2) with promising antiplasmodial activity against a chloroquine resistant (W2) Plasmodium falciparum strain with an IC50 of 2.8
±0.90 µg/mL for compound 1 and IC50 of 3.94±0.38 µg/mL for compound 2. Compounds 1 and 2 also exhibited moderate activity against the chloroquine sensitive (D6) Plasmodium falciparum strain with IC50 of 7.03±0.60 and 10.64±4.50 µg/mL, respectively. Conclusion: The results provide proof to support the use of G. buchananii by the indigenous community for antimalarial therapy.
Scholar articles
Antiplasmodial Biflavanones from the Stem Bark of Garcinia buchananii Engl.
RA Omole, MJ Moshi, M Heydenreich, HM Malebo… - Pharmacognosy Communications, 2019
All 4 versions

Kamau, RW, Midiwo JO, Mgani QA, Masila VM, Omosa LK, Bwire RN, Jacob MR, Wiggers FT, Muhammad I.  2019.  Oleanolic Acid and other Compounds Isolated from Cordia africana Lam which Inhibit Vancomycin Resistant Enterococcus. Pharmacognosy Communications. 9(6):91-95. Abstract

ABSTRACT
Introduction: Treatment of microbial infections has become complicated
due to increased resistance of microbes to the current drugs. The current
study investigates crude extracts and seven compounds from root and
stem bark of Cordia africana Lam. for antimicrobial and cytotoxic activity.
Methods: Extraction was done using 50% methanol in dichloromethane,
followed by chromatographic separation of compounds, whose structures
were established by interpretation of spectroscopic data. The in vitro
susceptibility of selected microbes to the crude extracts and pure compounds was determined. Cytotoxicity of 1, 6 and 7 was determined against
the drug sensitive, CCRF-CEM and resistant CEM/ADR-5000 cells, with
doxorubicin used as the standard. Results: The root bark extract of
C. africana yielded six known compounds: oleanolic acid (1), 3-β-lup-20(29)-
en-3-ol (2) stigmast-5,22-dien-3β-ol (3), 2-(2Z) -(3-hydroxy-3,7-dimethylocta2,6-dienyl)-1,4-benzenediol (4), 4-hydroxy-3-methoxy- benzaldehyde (5)
and 7-hydroxy-4′-methoxyisoflavone (6). The stem bark extract resulted to
1 and 2 alongside, ubiquinone-8 (7) and 1-octacosanol (8). Compound 1
showed moderate activity against Enterococcus faecium (IC50 of 14.44 µg/
mL), with vancomycin being inactive. Compounds 1, 6 and 7 showed cell
viability >50% against CEM/ADR5000 and CCRF-CEM cells at 10 µM and
therefore were considered inactive. Surprisingly, 1 was relatively more active compared to the standard, with cell viability of 57.93% against CEM/
ADR5000, versus 78.97% for doxorubicin. Conclusion: To the best of our
knowledge, this is the first report of the eight compounds from C. africana.
The cytotoxicity of 1, 6 and 7 are reported here for the first time. Traditional
use of the plant extract in management of various infections may be attributed to presence of 1, which displayed moderate antimicrobial activity.
Key words: Cordia africana, Ubiquinone-8, Oleanolic acid acid, 7-hydroxy4′-methoxyisoflavone, VRE.
Correspondence:
Rahab W. Kamau
Department of Chemistry, Masinde Muliro University of Science and Technology, P.O. Box 190-50100-Kakamega, KENYA.

Kuete, V, Omosa LK, Midiwo JO, Karaosmanoğlu O, Sivas H.  2019.  Cytotoxicity of 11 naturally occurring phenolics and terpenoids from Kenyan flora towards human carcinoma cells. Journal of Ayurveda and integrative medicine. 10(3):178-184. AbstractJournal article

Description
Background
Cancer constitutes a major hurdle worldwide and its treatment mainly relies on chemotherapy.
Objectives
The present study was designed to evaluate the cytotoxicity of eleven naturally occurring compounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normal CRL2120 fibroblasts.
Materials and methods
The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) was measured by spectrophotometry.
Results
Chalcones: 2′,4′-dihydroxy-6′-methoxychalcone (1); 4′,6′-dihydroxy-2′,5′-dimethoxychalcone (2); 2′,4 …

Efferth, T, Banerjee M, Abu-Darwish MS, Abdelfatah S, Böckers M, Bhakta-Guha D, Bolzani V, Daak S, Demirezer LÖmür, Dawood M, Efferth M, El-Seedi HR, Fischer N, Greten HJ, Hamdoun S, Hong C.  2019.  Biopiracy versus One-World Medicine–From colonial relicts to global collaborative concepts. Phytomedicine. 53:319-331. Abstract

Background
Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism.
Hypothesis
The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe.
Study design
Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of …

Omosa, LK, Mbogo GM, Korir E, Omole R, Ean-JeongSeo, Yenesew A, Heydenreich M, Midiwo JO, Efferth T.  2019.  Cytotoxicity of fagaramide derivative and canthin-6-one from Zanthoxylum (Rutaceae) species against multidrug resistant leukemia cells. Natural product research. :1-8. Abstract

In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 μM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia …

Omole, RA, Moshi MJ, Heydenreich M, Malebo HM, Gathirwa JW, Ochieng SA, Omosa LK, Midiwo JO.  2019.  Two lignans derivatives and two fusicoccane diterpenoids from the whole plant of Hypoestes verticillaris (LF) Sol. Ex roem. & schult. Phytochemistry Letters. 30:194-200. Abstract

Bioassay-guided screening of Hypoestes verticillaris whole plant CH2Cl2:MeOH (1:1) extract for anti-plasmodial activity yielded four new compounds: two lignans 2, 6-dimethoxysavinin (1), 2,6-dimethoxy-(7E)-7,8-dehydroheliobuphthalmin (2); and two fusicoccane diterpenoids: 11(12)-epoxyhypoestenone (3) and 3(11)-epoxyhypoestenone (4). The chemical structures were determined using various spectroscopic techniques: UV–vis, IR, CD, 1D, 2D and MS. Two fractions (RAO-43B and RAO-43D) and the isolated compounds were tested for activity against CQ susceptible (D6) and resistant (W2) Plasmodium falciparum parasite strains, in vitro and the IC50 values determined. While the whole extract and some resultant fractions displayed moderate activity, the isolated compounds exhibited mild anti-plasmodial activity against the both strains ranging from IC50 value of 328 μM in 1 to 93 μM in 3 against W2 strain.

Onyango, DW, Midiwo JO.  2019.  In vivo Evaluation of Anti-malarial Activity of Stem and Root Extracts of Erythrina abyssinica. European Journal of Medicinal Plants. 27(4):Page: 1-5. Abstract

Aims: The aim of the study was to determine the in vivo anti-malarial activity of stem and root extracts of E. abyssinica using the 4-day suppressive in vivo anti-malarial test.
Methodology: Female mice weighing approximately 20±2 g were intra-peritoneally injected with mice passaged Plasmodium berghei parasites. The extracts were then administered orally 2 h post-infection and, subsequently, daily for 4 days. On the 4 th day, blood smears were prepared from all the mice, stained with giemsa and parasitaemia as well as chemosuppression determined.
Results: Comparatively, the root extracts exhibited higher chemosuppression than stem extracts and the level of chemosuppression was dose dependent being the highest at 50 mg/kg and lowest at 12.5 mg/kg. Survival time in extract treated and chloroquine treated groups was 2 to 3 fold higher than the–ve control.
Conclusion: These findings suggest that the root extracts are more efficacious in suppressing the development of full blown malaria compared to stem extracts and may be a useful candidate in managing malaria in future.

2018

Omole, RA, Malebo HM, Nondo RSO, Katani S, Mbugi H, Midiwo J, Moshi MJ.  2018.  In vivo Anti-plasmodial Activity of Crude Extracts of Three Medicinal Plants Used Traditionally for Malaria Treatment in Kenya. European Journal of Medicinal Plants. 24(4):1-7. Abstract

The aim of the study was to determine the in vivo anti-plasmodial activity of three plants Rhamnus prinoides, Rubus keniensis and Garcinia buchananii which are used for malaria treatment by indigenous communities in Kenya. This work was done at the Department of Biological and Preclinical studies, Institute of Traditional Medicine, Muhimbili University of Health & Allied Sciences in October 2016 to August 2017. Male and female albino mice were infected with Plasmodium berghei (ANKA) in the Peter’s four day suppression test. Five groups of mice; Group 1 (solvent: 5 mL/kg body weight of 1% carboxymethyl cellulose), Group 5 (10 mg/kg body weight chloroquine), Groups 2, 3 and 4 were given 200, 400 and 800 mg/kg body weight of plant extracts. The results showed that 5% aqueous methanol extracts of R. prinoides, G. buchananii and R. keniensis exhibited higher anti-plasmodial activity than the 1:1 dichloromethane: methanol extracts in the preliminary testing. The doses showing 50% parasite suppression (EC50) were 139.2, 169.4 and 245.1 mg/kg body weight for R. prinoides, G. buchananii and R. keniensis, respectively. In vivo anti-plasmodial activity of the three plants has supported the traditional use of extracts of Rhamnus prinoides, Rubus keniensis and Garcinia buchananii for treatment of malaria. Isolation of compounds from these plants is in progress.

2017

Gichamba, A, Wagacha PW, Ochieng DO.  2017.  An Assessment of e-Extension Platforms in Kenya. International Journal of Innovative Studies in Sciences and Engineering Technology (IJISSET). 3:36-40. Abstract

The use of ICT in agriculture within developing countries has quickly gained popularity among development agencies, the private sector and even the government. ICT for agriculture (ICT4Ag) services such as trade platforms, notification platforms and advisory/extension services have been developed. This has been catalyzed by the growing number of farmers with access to ICT devices such as mobile phones. Among the available services, advisory/extension platforms have gained popularity among farmers and agriculture stakeholders in the developing world. These platforms have proven to be of importance to farmers who are curious about new farming methodologies, strategies to improve their yields, breeding techniques, among other factors. The ICT platforms employed include SMS, mobile applications, Interactive Voice Response systems, social media platform such as Facebook and Twitter, chat applications such as Whatsapp, blogs, radio programs and tv programs. The aim of this research was to assess the e-Extension platforms used in Kenya, whose purpose is to advise millions of farmers across different parts of the country using ICT platforms. 28 government e-Extension officers employed to advise farmers using ICT platforms were interviewed. The officers represented 15 different counties in Kenya. The study made important findings that would inform the government, agriculture extension content providers, and other stakeholders on critical aspects to be considered in deploying and managing eextension platforms among a population of diverse users within a developing country.

Ren, Y, Gallucci JC, Kinghorn DA.  2017.  An Intramolecular CAr–H••• O= C Hydrogen Bond and the Configuration of Rotenoids. Planta medica. 83(14/15):1194-1199. Abstract

Over the past half a century, the structure and configuration of the rotenoids, a group of natural products showing multiple promising bioactivities, have been established by interpretation of their NMR and electronic circular dichroism spectra and confirmed by analysis of single-crystal X-ray diffraction data. The chemical shift of the H-6′ 1H NMR resonance has been found to be an indicator of either a cis or trans C/D ring system. In the present study, four structures representing the central rings of a cis-, a trans-, a dehydro-, and an oxadehydro-rotenoid have been plotted using the Mercury program based on X-ray crystal structures reported previously, with the conformations of the C/D ring system, the local bond lengths or interatomic distances, hydrogen bond angles, and the H-6′ chemical shift of these compounds presented. It is shown for the first time that a trans-fused C/D ring system of rotenoids is preferred for …

Kama-Kama, F, Omosa LK, Nganga J, Maina N, Osanjo G, Yaouba S, Ilias M, Midiwo J, Naessens J.  2017.  Antimycoplasmal Activities of Compounds from Solanum aculeastrum and Piliostigma thonningii against Strains from the Mycoplasma mycoides Cluster. Frontiers in pharmacology. 8:920. Abstract

Infections caused by Mycoplasma species belonging to the ‘mycoides cluster’ negatively affect the agricultural sector through losses in livestock productivity. These Mycoplasma strains are resistant to many conventional antibiotics due to the total lack of cell wall. Therefore there is an urgent need to develop new antimicrobial agents from alternative sources such as medicinal plants to curb the resistance threat. Recent studies on extracts from Solanum aculeastrum and Piliostigma thonningii revealed interesting antimycoplasmal activities hence the motivation to investigate the antimycoplasmal activities of constituent compounds. The CH2Cl2/MeOH extracts from the berries of S. aculeastrum yielded a new β-sitosterol derivative (1) along with six known ones including; lupeol (2), two long-chain fatty alcohols namely undecyl alcohol (3) and lauryl alcohol (4); two long-chain fatty acids namely; myristic acid (5) and nervonic acid (6) as well as a glycosidic steroidal alkaloid; (25R)-3β-{O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranosyloxy-22α-N-spirosol-5-ene (7) from the MeOH extracts. A new furan diglycoside, (2,5-D-diglucopyranosyloxy-furan) (8) was also characterized from the CH2Cl2/MeOH extract of stem bark of P. thonningii. The structures of the compounds were determined on the basis of spectroscopic evidence and comparison with literature data. Compounds 1, 3, 4, 7 and 8 isolated in sufficient yields were tested against the growth of two Mycoplasma mycoides subsp. mycoides (Mmm), two M.mycoides. capri (Mmc) and one M. capricolum capricolum (Mcc) using broth dilution methods, while the minimum …

Omosa, LK, Midiwo JO, Kuete V.  2017.  Curcuma longa. Medicinal Spices and Vegetables from Africa Therapeutic Potential against Metabolic, Inflammatory, Infectious and Systemic Diseases. :425.: Academic Press Abstract

Curcuma longa L. (Zingiberaceae), commonly known as turmeric, is native to Southwest India with its rhizomes being the source of a bright yellow spice with various medicinal applications. It is widely cultivated throughout the tropics and similarly used for it medicinal value, in the cosmetic industry, and as a dye. Herein, the medicinal potentials of this plant as well as that of one of its bioactive constituents, curcumin, has been compiled. Turmeric can be regarded as a drug for the management of many diseases, such as cancer, inflammations, microbial infections, diabetes, arthritic, muscular disorders, biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, and sinusitis. Curcumin also displayed various pharmacological activities including antioxidant, antineoplastic, antiviral, antiinflammatory, antibacterial, antifungal, antidiabetic, anticoagulant, antifertility, cardiovascular protective, hepatoprotective, and immunostimulant activities in animals. This chapter provides baseline information to encourage the use of this plant in the management of various human ailments.

Mota, SF, Oliveira DF, Heleno VCG, Soares ACF, Midiwo JO, Souza EA.  2017.  Methyl and p-Bromobenzyl Esters of Hydrogenated Kaurenoic Acid for Controlling Anthracnose in Common Bean Plants. Journal of Agricultural and Food Chemistry. 65(8):1489-1495. AbstractFull text link

Kaurenoic acid derivatives were prepared and submitted to in vitro assays with the fungus Colletotrichum lindemuthianum, which causes anthracnose disease in the common bean. The most active substances were found to be methyl and p-bromobenzylesters, 7 and 9, respectively, of the hydrogenated kaurenoic acid, which presented a minimum inhibitory concentration (MIC) of 0.097 and 0.131 mM, respectively, while the commercial fungicide methyl thiophanate (MT) presented a MIC of 0.143 mM. Substances 7 (1.401 mM) and 9 (1.886 mM) reduced the severity of anthracnose in common bean to values statistically comparable to MT (2.044 mM). According to an in silico study, both compounds 7 and 9 are inhibitors of the ketosteroid isomerase (KSI) enzyme produced by other organisms, the amino acid sequence of which could be detected in fungal genomes. These substances appeared to act against C. lindemuthianum by inhibiting its KSI. Therefore, substances 7 and 9 are promising for the development of new fungicides.
Keywords: Colletotrichum lindemuthianum; ent-kauran-18-oic acid methyl ester; ent-kauran-18-oic acid p-bromobenzyl ester; fungicide; ketosteroid isomerase

Samita, F, Ochieng CO, Owuor PO, Manguro LOA, Midiwo JO.  2017.  Isolation of a new β-carboline alkaloid from aerial parts of Triclisia sacleuxii and its antibacterial and cytotoxicity effects. Natural product research. 31(5):529-536. AbstractFull text link

A new β-carboline alkaloid named sacleuximine A (1) together with known compounds palmatine (2), isotetrandrine (3), trans-N-feruloyltyramine (4), trans-N-caffeoyltyramine (5), yangambin (6), syringaresinol (7), sesamin (8), (+) epi-quercitol (9), 4-hydroxybenzaldehyde (10), β-sitosterol (11), quercetin 3-O-rutinoside (12) and myricetin 3-O-β-glucose (1→6) α-rhamnoside (13) have been isolated from methanol extract of Triclisia sacleuxii aerial parts. Compounds 1–10 were evaluated for their cytotoxicity against human adenocarcinoma (HeLa), human hepatocarcinoma (Hep3B) and human breast carcinoma (MCF-7) cells lines and also for antibacterial activities against both Gram-positive and Gram-negative bacteria. The cytotoxicity (IC50) values ranged between 0.15 and 36.7 μM while the minimum inhibitory concentrations were found to be in the range of 3.9 and 125 μM, respectively. This is the first report of antibacterial compounds and the isolation of lignans together with a β-carboline alkaloid from T. sacleuxii.
Keywords: Triclisia sacleuxii, Menispermaceae, secondary metabolites, cytotoxicity, antibacterial, aerial parts

Soares, ACF, Cabral MMW, Martins CHG, Ferreira AE, Bergamo PAS, Omosa LK, Midiwo JO, Parreira RLT, Heleno VCG.  2017.  Study of Anti-Tuberculosis Activity Behaviour of Natural Kaurane and Trachylobane Diterpenes Compared with Structural Properties Obtained by Theoretical Calculations. Natural Product Communications. 12(5):763-769. AbstractFull text

A set of seven diterpenes, three kauranes and four trachylobanes, isolated from the African plant Psiadia punctulata were assayed against Mycobacterium tuberculosis and reached activity comparable with cycloserine, a second line drug used to treat tuberculosis (TB). Several structural properties of those diterpenes, such as lipophilicity, HOMO and LUMO energies, charge density, and intramolecular hydrogen bond (IHB) formation, were obtained by theoretical calculations and compared with their activities. Peculiar correlations were observed, especially between activity, lipophilicity and IHB formation.

Study of anti-tuberculosis activity behaviour of natural kaurane and trachylobane diterpenes compared with structural properties obtained by theoretical calculations (PDF Download Available). Available from: https://www.researchgate.net/publication/317750342_Study_of_anti-tuberculosis_activity_behaviour_of_natural_kaurane_and_trachylobane_diterpenes_compared_with_structural_properties_obtained_by_theoretical_calculations [accessed Sep 25, 2017].

Aldhaher, A, Langat M, Ndunda B, Chirchir D, Midiwo JO, Njue A, Schwikkard S, Carew M, Mulholland D.  2017.  Diterpenoids from the roots of Croton dichogamus Pax. Phytochemistry. 144:1-8. AbstractFull text

Four previously undescribed diterpenoids including two crotofolanes, crotodichogamoin A and B, and two halimanes, crothalimene A and B, a new sesquiterpenoid, and fifteen previously reported compounds, including the crotofolane, crotohaumanoxide, the casbane, depressin, a further seven furanohalimane diterpenoids, three patchoulane and two further cadinane sesquiterpenoids and aleuritolic acid were isolated from the root of Croton dichogamus. Crotodichogamoin B is an important biosynthetic intermediate of the crotofolane class and this is the first report of patchoulene sesquiterpenoids from the genus. Compounds were tested at one concentration, 1 × 10−5 M, in the NCI59 cell one-dose screen but did not show significant activity snd were also evaluated for their cytotoxicity against Caco-2 cell lines using the neutral red assay. 10-epi-Maninsigin D reduced Caco-2 cell viability at 10, 30 and 100 μM, with values of decreased viability of 28%, 48% and 43% respectively. None of the other tested compounds showed significant activity.
Keywords
Croton dichogamusEuphorbiaceaeCrotofolaneCrotodichogamoin BCrothalimene ACrothalimene BPatchoulaneCaco-2 cell viability

2016

Ndunda, B, Langat MK, Mulholland DA, Eastman H, Jacob MR, Khan SI, Walker LA, Muhammad I, Kerubo LO, Midiwo JO.  2016.  New ent-Clerodane and Abietane Diterpenoids from the Roots of Kenyan Croton megalocarpoides Friis & MG Gilbert. Planta medica. 82(11/12):1079-1086. AbstractFull text link

The roots of the endangered medicinal plant Croton megalocarpoides collected in Kenya were investigated and twenty-two compounds isolated. Among them were twelve new ent-clerodane (1–12) and a new abietane (13) diterpenoids, alongside the known crotocorylifuran (4 a), two known abietane and four known ent-trachylobane diterpenoids, and the triterpenoids, lupeol and acetyl aleurotolic acid. The structures of the compounds were determined using NMR, HRMS and ECD. The isolated compounds were evaluated against a series of microorganisms (fungal and bacteria) and also against Plasmodium falciparum, however no activity was observed.
Key words:
Croton megalocarpoides - Euphorbiaceae - abietane - ent-clerodane - ent-trachylobane - diterpenoids - electronic circular dichroism

Schrader, KK, Cantrell CL, Midiwo JO, Muhammad I.  2016.  Compounds from Terminalli brownii Extracts with Toxicity against the Fish Pathogenic Bacterium Flavobacterium columnare. Natural Product Communications . 11(11):1679-1682. AbstractFull text link

Interpretive Summary:

A rapid bioassay was used to evaluate extracts from the stem bark of plant found in Kenya for antibacterial activities against fish pathogenic bacteria. Two natural compounds were isolated from the extracts and discovered to possess antibacterial activities against a species of fish pathogenic bacteria which causes a common disease in pond-raised catfish and several other species of freshwater fish.

Technical Abstract:

The pond-raised channel catfish (Ictalurus punctatus) industry in the United States of America can incur losses of over a $100 million annually due to bacterial diseases including columnaris disease caused by Flavobacterium columnare. One management approach available to catfish producers is the use of medicated-feed containing antibiotics. However, the negative attributes of antibiotic use in agriculture include public concerns and the potential development of antibiotic-resistant bacteria. Therefore, the discovery of environmentally-safe natural compounds for use as therapeutants would greatly benefit the catfish industry. In this study, a rapid bioassay was used to evaluate crude plant extracts as the first step in the discovery of natural therapeutants. Plant extracts from Terminalia brownii were found to be inhibitory towards F. columnare. The minimum inhibitory concentration (MIC) of the 5% water-methanol extract of T. brownii (stem bark) was 10 µg/mL and the 24-h 50% inhibition concentration (IC50) was 40 µg/mL. Subsequent bioassay-guided fractionation of the T. brownii ethanol extract using reverse phase C-4 chromatography revealed the highest level of activity in the aqueous:methanol (50:50) fraction. HPLC analysis and subsequent purification of this fraction provided two compounds identified as ellagic acid (1) and 4-O-(3'',4''-di-O-galloyl-a-L-rhamnopyranosyl)ellagic acid (2). Compound 2 was the most active isolated compound, with a minimum inhibitory concentration (MIC) of 10±0 µg/mL and 24-h 50% inhibition concentration (IC50) of 31±1 µg/mL. Although 1 was more active according to a MIC of 6±5 µg/mL, its 24-h IC50 was >100 µg/mL, and, therefore, it was less active overall between the two most active isolated compounds.

Kama-Kama, F, Midiwo J, Nganga J, Maina N, Schiek E, Omosa LK, Osanjo G, Naessens J.  2016.  Selected ethno-medicinal plants from Kenya with in vitro activity against major African livestock pathogens belonging to the “Mycoplasma mycoides cluster”. Journal of ethnopharmacology. 192:524-534. AbstractFull text link

Members of ‘Mycoplasma mycoides cluster’ are important ruminant pathogens in Africa. Diseases caused by these Mycoplasma negatively affect the agricultural sector especially in developing countries through losses in livestock productivity, mortality and international trade restrictions. There is therefore urgent need to develop antimicrobials from alternative sources such as medicinal plants to curb these diseases. In Kenya, smallholder farmers belonging to the Maasai, Kuria and Luo rely on traditional Kenyan herbals to treat respiratory symptoms in ruminants. In the current study extracts from some of these plants were tested against the growth of members of Mycoplasma mycoides cluster.
Aim

This study aimed at identifying plants that exhibit antimycoplasmal activities using an ethnobotanical approach.

Materials and methods

Kenyan farmers of Maasai, Luo and Kuria ethnic groups were interviewed for plant remedies given to livestock with respiratory syndromes. The plant materials were thereafter collected and crude extracts prepared using a mixture of 50% of methanol (MeOH) in dichloromethane (CH2Cl2), neat methanol (MeOH), ethanol (EtOH) and water to yield four crude extracts per plant part. The extracts were tested in vitro against five strains of Mycoplasma mycoides subsp. capri, five strains of Mycoplasma mycoides subsp. mycoides and one strain of Mycoplasma capricolum subsp capricolum using broth micro-dilution assays with an initial concentration of 1 mg/ml. Minimum inhibitory concentration (MIC) of the most active extracts were determined by serial dilution.
Results

Extracts from five plants namely: Solanum aculeastrum, Albizia coriaria, Ekebergia capensis, Piliostigma thonningii and Euclea divinorum exhibited the highest activities against the Mycoplasma strains tested. Mycoplasma mycoides subsp. mycoides were more susceptible to these extracts than Mycoplasma mycoides subsp. capri and Mycoplasma capricolum susp. capricolum. The activities of the crude extracts varied with the solvent used for extraction. The MICs mean values of the active extracts varied from 0.02 to 0.6 mg/ml.
Conclusions

The results suggested that these plants could potentially contain antimicrobial compounds that might be useful for the treatment of respiratory diseases in ruminants. Future work should focus on the isolation and identification of the active compounds from the plant extracts that showed interesting activities and evaluation of their antimicrobial and cytotoxic potential.
Mycoplasma mycoidesEthnobotanyAntimicrobial activityLivestockEthno-medicinal from plants from Kenya

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. AbstractFull text link

In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3′ together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4–64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are substrates of bacterial efflux pumps and therefore should be combined to efflux pump inhibitors in the fight against MDR bacterial infections.

Keywords:

Anthraquinones Benzoquinones Chalcones Antibacterial activities Multidrug resistance Efflux pump inhibitor

Langat, MK, Crouch N, Ndunda B, Midiwo JO, Aldhaher A, Alqahtani A, Mulholland DA.  2016.  The Chemistry of African Croton species. Planta Medica. 81(S 01):384. AbstractFull text link

The genus Croton is one of the largest of Euphorbiaceae sensu stricto, and consists of over 1300 species of trees, shrubs and herbs that are distributed worldwide in the warm tropics and subtropics. It is reported that 124 Croton species occur in continental Africa whilst a further 156 species are endemic to Madagascar. Another 12 species occur in the Indian Ocean islands of Comoros, Mauritius, Reunion and Sao Tome and Principe [1]. We discuss the chemistry, chemotaxonomic patterns and biological activities of selected compounds from ten African Croton taxa: C. alienus, C. dichogamus, C. gratissimus var. gratissimus, C. megalobotrys, C. megalocarpoides, C. megalocarpus, C. menyhartii, C. pseudopulchellus, C. rivularis and C. sylvaticus. Examples of compounds to be presented include cembranoids (1-3) from C. gratissimus var. gratissimus [2,3], ent-kauranes (4-5) from C. pseudopulchellus [4], ent-clerodanes (6-8) from C. sylvaticus, C. megalocarpus and C. megalocarpoidies, and both halimanes (9) and crotofolanes (10 – 11) from C. dichogamus. Triterpenoids, sesquiterpenoids, flavonoids and cyclohexanol derivatives from Croton will also be discussed. Selected cembranoids from C. gratissimus were tested against a chloroquine-sensitive strain of Plasmodium falciparum (D10) and against the PEO1 and PEO1TaxR ovarian cancer cell lines [2]. Compound 1 showed moderate activity against the PEO1 (IC50= 132 nM) and PEO1TaxR (IC50= 200 nM) ovarian cancer cell lines. Selected ent-kauranoids were tested for their effects on Semliki Forest Virus replication and for cytotoxicity against human liver tumour cells (Huh-7 strain). Other Croton-derived compounds were tested for antimicrobial and antifungal activities [5,6], antiplasmodial activity using two strains of Plasmodium falciparum, antileishmanial activities against Leishmania donovanii [5], and cytotoxic activity against NCI59 cancer cell panels, and colorectal and VERO cancer cell lines.
Keywords: Croton, Euphorbiaceae, ent-clerodanes, cembranoids, crotofolanes

Kuete, V, Omosa LK, Tala VSR, Midiwo JO, Mbaveng AT, Swaleh S, Karaosmanoğlu O, Sivas H.  2016.  Cytotoxicity of plumbagin, rapanone and 12 other naturally occurring quinones from Kenyan flora towards human carcinoma cells. BMC Pharmacology and Toxicology. 17(1):60. AbstractFull text link

Background
Cancer is a major public health concern globally and chemotherapy remains the principal mode of the treatment of various malignant diseases.

Methods
This study was designed to investigate the cytotoxicity of 14 naturally occurring quinones including; 3 anthraquinones, 1 naphthoquinone and 10 benzoquinones against 6 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspases activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) were measured by spectrophotometry.

Results
Anthraquinone: emodin (2), naphthoquinone: plumbagin (4), and benzoquinones: rapanone (9), 2,5-dihydroxy-3-pentadecyl-2,5-cyclohexadiene-1,4-dione (10), 5-O-methylembelin (11), 1,2,4,5-tetraacetate-3-methyl-6-(14-nonadecenyl)-cyclohexadi-2,5-diene (13), as well as doxorubicin displayed interesting activities with IC50 values below 100 μM in the six tested cancer cell lines. The IC50 values ranged from 37.57 μM (towards breast adenocarcinoma MCF-7 cells) to 99.31 μM (towards small cell lung cancer A549 cells) for 2, from 0.06 μM (MCF-7 cells) to 1.14 μM (A549 cells) for 4, from 2.27 μM (mesothelioma SPC212 cells) to 46.62 μM (colorectal adenocarcinoma DLD-1 cells) for 9, from 8.39 μM (SPC212 cells) to 48.35 μM (hepatocarinoma HepG2 cells) for 10, from 22.57 μM (MCF-7 cells) to 61.28 μM (HepG2 cells) for 11, from 9.25 μM (MCF-7 cells) to 47.53 μM (A549 cells) for 13, and from 0.07 μM (SPC212 cells) to 1.01 μM (A549 cells) for doxorubicin. Compounds 4 and 9 induced apoptosis in MCF-7 cells mediated by increased ROS production and MMP loss, respectively.

Conclusion
The tested natural products and mostly 2, 4, 9, 10, 11 and 13 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma.

Keywords

Carcinoma cytotoxicity Mode of action Plumbagin Quinones Rapanone

2015

Irungu, BN, Adipo N, Orwa JA, Kimani F, Heydenreich M, Midiwo JO, Björemark PM, Håkansson M, Yenesew A, Erdélyi Máté.  2015.  Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica. Journal of Ethnopharmacology. 174:419-425. AbstractJournal Article

Ethnopharmacological relevance
Turraea robusta and Turraea nilotica are African medicinal plants used for the treatment of a wide variety of diseases, including malaria. The genus Turraea is rich in limonoids and other triterpenoids known to possess various biological activities.

2014

Omosa, LK, Amugune B, Ndunda B, Milugo TK, Heydenreich M, Yenesew A, Midiwo JO.  2014.  Antimicrobial flavonoids and diterpenoids from Dodonaea angustifolia. South African Journal of Botany. Abstract

The surface exudates of the leaves of Dodonaea angustifolia from Ngong forest population (6 km from Nairobi city center, Kenya) demonstrated antimicrobial activity against Gram-negative (Escherichia coli), Gram-positive (Staphylococcus aureus and Bacillus pumilus) bacteria and the fungus Sacchromyces cerevisiae. Chromatographic separation of the exudates yielded eight methylated flavonoids; 5-hydroxy-3, 4′,7-trimethoxyflavone (1), 3,5-dihydroxy-4′,7-dimethoxyflavone (2), santin (3), kumatakenin (4), rhamnocitrin (5), isokaempferide (6), 3,4′,5,7, tetrahydroxy-6-methoxyflavone (7), pinocembrin (8); two clerodanes, dodonic acid (9) and 2β-hydroxyhardwickiic acid (10) and one labdane; (ent-3β,8α)-15,16-epoxy-13(16),14-labdadiene-3,8-diol (11) diterpenoids. The flavonoid aglycones; 6, 7 and the clerodane diterpenoids; 9 and 10 and labdane diterpenoid, 11 were isolated for the first time from this plant species. The structures of the isolated compounds were identified using ultraviolet (UV), mass spectroscopy (MS), one dimension (1D) and two dimension (2D) nuclear magnetic resonance (NMR) spectroscopy and by comparison of the spectral data with literature. The quercetin derivative, 3,4′,5-trihydroxy-3′,7-dimethoxyflavone (12) showed broad spectrum antibacterial activities against E. coli and B. pumilus with minimum inhibition concentration (MIC) values less than 31.25 μg/well and against S. aureus with MIC below 62.5 μg/well. This compound showed poor antifungal activity against S. cerevisiae (MIC < 500 μg/well). Good antifungal activities were observed for 5,4′-dihydroxy-7-methoxyflavanone (13) and hautriwaic acid lactone (14) against S. cerevisiae with MIC values less than 7.8 μg/well. The most active antifungal compound was 5,7-dihydro-3,4′,6-trimethoxyflavone (3, santin) with an MIC value less than 3.9 μg/well against S. cerevisiae. The rest of the compounds exhibited weak to moderate activities. For comprehensive structure activity relationship studies (SAR), hautriwaic acid lactone (14), hautriwaic acid (15), penduletin (16) isolated from the surface exudates of D. angustifolia from Voi (200 km from Mombasa city center, Kenya) and 12 and 13 from Senecio roseiflorus isolated earlier were included in the bioassays.

2013

Machumi, F, Midiwo JO, Jacob MR, Khan SI, Tekwani BL, Walker LA, Muhammad I.  2013.  Phytochemical, Antiparasitic and Antimicrobial Investigations of Terminalia brownii. AbstractPhytochemical, Antiparasitic and Antimicrobial Investigations of Terminalia brownii

Terminalia brownii is an African medicinal plant used to treat parasitic and microbial infections [1]. Chromatographic separations on the stem bark extract aimed at identifying the active components led to isolation of a new oleanane-type triterpenoid, along with seven known oleanane-type triterpenoids and seven ellagic acid derivatives. The new compound was identified using spectroscopic methods as 3β,24-O-ethylidenyl-2α,19α-dihydroxyolean-12-en-28-oic acid (1). The compounds were evaluated for their antiplasmodial, antileishmanial and antimicrobial activities giving the most potent antiplasmodial activity with IC50 values of 2.76 µg/mL for 23-galloylarjunolic acid (2) against P. falciparum W2 strain and the most potent antimicrobial activity with IC50 values of 0.32 µg/mL for diellagic lactone (3) against C. glabrata.

2012

Machumi, F, Yenesew A, Midiwo JO, Heydenreich M, Kleinpeter E, Khan S, Tekwani BL, Walker LA, Muhammad I.  2012.  Antiparasitic and anticancer carvotacetone derivatives from Sphaeranthus bullatus. Website

2011

Waters, NC, Midiwo JO, Yenesewa A, Akala HM, Kiremire BT, Derese S, Evase FL.  2011.  Antiplasmodial and Radical Scavenging Activities of flavonoids from Kenyan Erythrina species. antiplasmodial_and_radical_...0001.pdfWebsite
Midiwo, JO, Yenesew A, Aluoch A 0, Avoo JA.  2011.  Alkaloids and lignans from zanthoxylum usambarense and zanthoxylum chalybeum. Website

2010

Midiwo, JO, Yenesew A, Juma BF, Omosa KL, Omosa IL, Mutisya D.  2010.  Phytochemical Evaluation of So me Kenyan Medicinal Plants. AbstractPhytochemical Evaluation of So me Kenyan Medicinal Plants

11 th NAPRECA Symposium Book of Proceedings, Antananarivo, Madagascar Pages 9-19 Midiwo et al. 9 Phytochemical Evaluation of So me Kenyan Medicinal Plants J. Ogweno Midiwo, A. Yenesew, B.F. Juma Kerubo L Omosa, Irene L Omosa, Daniel Mutisya. Department of Chemistry, University of Nairobi, P.o. Box 30197, Nairobi. Kenya. E-mail: jmidiwo@uonbi.ac.ke Abstract There are more than 1200 described medicinal pl ants in Kenya from a flora of approximately 10,000 members. Strong cross-medical informati on from the 42 ethnic groups points to the high potential of some of these species. The Myrsinaceae are well established ethno-anthel mintics and anti-bacterials. They are harbingers of long alkyl side chain benzoquinones which clearly have a protective function from their histochemical disposition. The main benzoqui none in the sub-family Myrsinodae is embelin while for the Maesodae it is maesaquinone together with its 5-acetyl derivative; the distribution of these benzoquinones by their alkyl side chain le ngth or the presence / absence of 6-methyl group is in accord with morphological sub-fam ily de-limitation. The benzoquinones showed anti- feedant, anti-microbial, phytotoxic, acaricidal, in secticidal and nematicidal activity. Many other benzoquinones of medium and mi nor concentration were also isolated and characterised. Some plants belonging to the Polygonaceae which are widely used as ethno-anthelmintics have been studied. The common anthelmintic anthraquinones were obtained from all five Rumex species while the naphthalenic acetogenin deriva tive, nepodin was more selectively distributed. The leaf of Polygonum senegalense is upto 17% surface exudate; about thirteen non polar flavonoid derivatives (chalcones, di hydrochalcones, flavanones and a flavone) have been isolated from it. From the internal aerial tissues of this plant, the major flavonoids were common flavonoids, quercetin, kaempferol, luteolin a nd their glycosides. The only unique compound isolated from this plant was 2'-glucosy l-6'-hydroxy-4'-methoxychalcone whose aglycone, uvangolatin is part of the exuda te mixture. Other leaf exuda te plants studied included the stomach-ache medicine, Psiadia punctulata (Compositae) from which novel methylated flavonoids, kaurene and trachyloba n diterpenes have been found.

Dr. Derese, S, Omosa LK, Midiwo JO, Yenesew A, Peter MG, Heydenreich. M.  2010.  neo-Clerodane diterpenoids from the leaf exudate of Dodonaea angustifolia. Abstractneo-Clerodane diterpenoids from the leaf exudate of Dodonaea angustifolia

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

2009

Martin, PG, Yenesew A, Heydenreich M, Guchu SM, lrungu B, Derese S, Midiwo JO.  2009.  Flavonoids and isoflavonoids of Erythrina burttii. isoflavanoes_...0001.pdfWebsite

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