Publications

Found 28 results

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2020
Owor RO, Bedane KG, Zühlke S, Derese S, Ong’amo GO, Ndakala A, Spiteller M. "Anti-inflammatory Flavanones and Flavones from Tephrosia linearis." Journal of Natural Products. 2020;83(4):996-1004. AbstractJournal of Natural Products

Description
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 …

Andima M, Coghi P, Yang LJ, Wong VKW, Ngule CM, Heydenreich M, Ndakala AJ, Yenesew A, Derese S. "Antiproliferative Activity of Secondary Metabolites from Zanthoxylum zanthoxyloides Lam: In vitro and in silico Studies." Pharmacognosy Communications. 2020;10(1). AbstractPharmacognosy Communications

Description
Background: Plant derived compounds have provided proming leads in search for safer anticancer chemotherapies. Zanthoxylum zanthoxyloides is a common medicinal plant in Uganda whose bioactive composition has not been fully elucidated. The aim of this study was to evaluate the in vitro antiproliferative potential of compounds isolated from Zanthoxylum zanthoxyloides and their probable in silico anticancer mechanisms of action. Methods: Column chromatography was used to isolate compounds from MeOH: CH2Cl2 (1: 1) extract of the stem bark extract of Zanthoxylum zanthoxyloides. The structures of the isolated compounds were elucidated by NMR and MS analyses. MTT assay was used to measure cell viability. Using in silico docking, the interaction of the compounds with key target proteins in the p53 pathway was determined. Results: From the root bark of this plant five compounds were isolated, namely; dihydrochelerythrine (1), skimmianine (2), tridecan-2-one (3), sesamin (4) and hesperidin (5). Dihydrochelerythrine (1) inhibited proliferation of liver cancer (HCC) cells (IC50 21.2), breast cancer (BT549) cells,(IC50 21.2 μM). Similarly, sesamin (4) exhibited moderate inhibitory activity against BT549 cancer cells (IC50 47.6 μM). Hesperidin (5) showed low inhibitory activity against A549 and HEp2 (Larynx) cells but was significantly toxic to normal liver and lung cells.
In silico docking studies showed that all the compounds strongly bind to cyclin-dependent kinases (CDK2 and CDK6) and weakly bind to caspases 3 and 8 suggesting that they inhibit cancer cells by inducing cell cycle arrest and apoptosis. Conclusion: This study indicates …

Buyinza D, Chalo DM, Derese S, Ndakala A, Yenesew A. "Flavonoids and Isoflavonoids of Millettia dura and Millettia ferruginea: Phytochemical review and chemotaxonomic values." Biochemical Systematics and Ecology. 2020;91:104053. AbstractBiochemical Systematics and Ecology

Description
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 …

Owor RO, Bedane KG, Openda YI, Zühlke S, Derese S, Ong’amo G, Ong’amo G, Ndakala A, Spiteller M. "Synergistic anti-inflammatory activities of a new flavone and other flavonoids from Tephrosia hildebrandtii vatke." Natural Product Research. 2020:1-4. AbstractNatural Product Research

Description
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.

Masila VM, Ndakala AJ, Byamukama R, Midiwo JO, Kamau RW, Wang M, Kumarihamy M, Zhao J, Heydreich M, Muhammad I. "Synthesis, structural assignments and antiinfective activities of 3-O-benzyl-carvotacetone and 3-hydroxy-2-isopropyl-5-methyl-p-benzoquinone." Natural Product Research. 2020:1-9. AbstractNatural Product Research

Description
In an attempt to synthesize carvotacetone analogues, new 3-O-benzyl-carvotacetone (10) and previously reported 3-hydroxy-2-isopropyl-5-methyl-p-benzoquinone (11) were synthesized from piperitone (7). In this work, we describe the synthesis of 10 and other analogues from 7. Luche reduction of 7 to cis-piperitol (8), followed by benzylation yielded 3-O-benzyl-piperitol (9). Riley oxidation of 9 afforded corresponding ketone 10, 11 and 3-benzyloxy-4-isopropylcyclohex-1-enecarbaldehyde (12). Structures of these compounds were determined based on NMR, IR and LC-MS spectral data. Compound 11, exhibited antiplasmodial activities against chloroquine-sensitive (D6) and resistant (W2) strains of Plasmodium falciparum with IC50 values of 0.697 and 0.653 µg/mL, respectively. In addition, compound 11 was active against Cryptococcus neoformans with an IC50 value of 3.11 µg/mL, compared to reference …

2019
Adem FA, Kuete V, Mbaveng AT, Heydenreich M, Koch A, Ndakala A, Irungu B, Yenesew A, Efferth T. "Cytotoxic flavonoids from two Lonchocarpus species." Natural product research. 2019;33(18):2609-2617. AbstractNatural product research

Description
A new isoflavone, 4′-prenyloxyvigvexin A (1) and a new pterocarpan, (6aR,11aR)-3,8-dimethoxybitucarpin B (2) were isolated from the leaves of Lonchocarpus bussei and the stem bark of Lonchocarpus eriocalyx, respectively. The extract of L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2′-dimethoxy-3′,4′-methylenedioxyisoflavone, 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6aR,11aR)-maackiain and (6aR,11aR)-edunol. (6aR,11aR)-Edunol was also isolated from the stem bark of L. eriocalyx. The structures of the isolated compounds were elucidated by spectroscopy. The cytotoxicity of the compounds was tested by resazurin assay using drug-sensitive and multidrug-resistant cancer cell lines. Significant antiproliferative effects with IC50 values below 10 …

Adem FA, Mbaveng AT, Kuete V, Heydenreich M, Ndakala A, Irungu B, Yenesew A, Efferth T. "Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer." Phytomedicine. 2019;58:152853. AbstractPhytomedicine

Description
Background
While incidences of cancer are continuously increasing, drug resistance of malignant cells is observed towards almost all pharmaceuticals. Several isoflavonoids and flavonoids are known for their cytotoxicity towards various cancer cells.
Purpose
The aim of this study was to determine the cytotoxicity of isoflavones: osajin (1), 5,7-dihydroxy-4ˈ-methoxy-6,8-diprenylisoflavone (2) and biflavonoids: chamaejasmin (3), 7,7″-di-O-methylchamaejasmin (4) and campylospermone A (5), a dimeric chromene [diphysin(6)] and an ester of ferullic acid with long alkyl chain [erythrinasinate (7)] isolated from the stem bark and roots of the Kenyan medicinal plant, Ormocarpum kirkii. The mode of action of compounds 2 and 4 was further investigated.
Methods
The cytotoxicity of compounds was determined based on the resazurin reduction assay. Caspases activation was evaluated using the caspase-Glo assay. Flow …

Buyinza D, Yang LJ, Derese S, Ndakala A, Coghi P, Heydenreich M, Wong VKW, Möller HM, Yenesew A. "Cytotoxicity of isoflavones from Millettia dura." Natural Product Research. 2019:1-4. AbstractNatural Product Research

Description
The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 μM. Durmillone was the most active with IC50 values of 6.6 μM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 μM), LO2 hepatocytes (IC50 78.7 μM) and CCD19Lu fibroblasts (IC50 >100 μM).

2018
Adem FA, Kuete V, Mbaveng AT, Heydenreich M, Ndakala A, Irungu B, Efferth T, Yenesew A. "Cytotoxic benzylbenzofuran derivatives from Dorstenia kameruniana." Fitoterapia. 2018;128:26-30. AbstractFitoterapia

Description
Chromatographic separation of the extract of the roots of Dorstenia kameruniana (family Moraceae) led to the isolation of three new benzylbenzofuran derivatives, 2-(p-hydroxybenzyl)benzofuran-6-ol (1), 2-(p-hydroxybenzyl)-7-methoxybenzofuran-6-ol (2) and 2-(p-hydroxy)-3-(3-methylbut-2-en-1-yl)benzyl)benzofuran-6-ol(3) (named dorsmerunin A, B and C, respectively), along with the known furanocoumarin, bergapten (4). The twigs of Dorstenia kameruniana also produced compounds 1–4 as well as the known chalcone licoagrochalcone A (5). The structures were elucidated by NMR spectroscopy and mass spectrometry. The isolated compounds displayed cytotoxicity against the sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells, where compounds 4 and 5 had the highest activities (IC50 values of 7.17 μM and 5.16 μM, respectively) against CCRF-CEM leukemia cells. Compound 5 …

Andima M, Costabile G, Isert L, Ndakala AJ, Derese S, Merkel OM. "Evaluation of β-Sitosterol loaded PLGA and PEG-PLA nanoparticles for effective treatment of breast cancer: Preparation, physicochemical characterization, and antitumor activity." Pharmaceutics. 2018;10(2):232. AbstractPharmaceutics

Description
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 …

SCOLASTICA MANYIM, Ndakala AJ, Derese S. "Modeling and synthesis of antiplasmodial chromones, chromanones and chalcones based on natural products of Kenya." Biofarmasi Journal of Natural Product Biochemistry. 2018;16(1):8-21. AbstractBiofarmasi Journal of Natural Product Biochemistry

Description
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 …

2017
Atilaw Y, Muiva-Mutisya L, Ndakala A, Akala HM, Yeda R, Wu YJ, Coghi P, Wong VKW, Erdélyi Máté, Yenesew A. "Four Prenylflavone Derivatives with Antiplasmodial Activities from the Stem of Tephrosia purpurea subsp. leptostachya." Molecules. 2017;22(9):1514. AbstractMolecules

Description
Four new flavones with modified prenyl groups, namely (E)-5-hydroxytephrostachin (1), purleptone (2),(E)-5-hydroxyanhydrotephrostachin (3), and terpurlepflavone (4), along with seven known compounds (5–11), were isolated from the CH 2 Cl 2/MeOH (1: 1) extract of the stem of Tephrosia purpurea subsp. leptostachya, a widely used medicinal plant. Their structures were elucidated on the basis of NMR spectroscopic and mass spectrometric evidence. Some of the isolated compounds showed antiplasmodial activity against the chloroquine-sensitive D6 strains of Plasmodium falciparum, with (E)-5-hydroxytephrostachin (1) being the most active, IC 50 1.7±0.1 μM, with relatively low cytotoxicity, IC 50> 21 μM, against four cell-lines. View Full-Text

2016
Erick A, Omosa L, Midiwo J, Ndakala A, Mwaniki J. "Antioxidant Activities of Flavonoid Aglycoes from Kenyan Gardenia ternifolia Schum and Thonn." IOSR Journal of Pharmacy and Biological Sciences. 2016;11(3):136-141.
Manyim S. Modeling and synthesis of antiplasmodial chromones, chromanones and chalcones based on natural products of Kenya. Nairobi: University of Nairobi; 2016. Abstract

A significant amount of research has been done on plants of Kenya resulting in the isolation of thousands of natural products, but data on these natural products is not systematically organized in a readily accessible form. This has necessitated 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 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 an above average similarity among the top performing ligands in the docking studies with shape and electrostatic comparison. This led to the identification of compounds of interest which were targeted for synthesis and antiplasmodial assay. 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. Whereas 45 showed strong activity, 47 and 48 had moderate activity against the chloroquine resistant K1 strain of P. falciparum with IC50 values of 4.56±1.66, 17.62 ± 5.94 and 18.01 ±1.66 μg/ml, respectively. Since the synthesized compounds showed antiplasmodial potential, there is need for further computational refinement of these compounds to optimize their antiplasmodial activity.

2014
Atilaw Y, Heydenreich M, Ndakala A, Akala HM, Kamau E, Yenesew A. "3-Oxo-14α,15α-epoxyschizozygine: A new schizozygane indoline alkaloid from Schizozygia coffaeoides." Phytochemistry Letters. 2014;10:28-31.
Negera A, Matthias H, Midiwo JO, Ndakala A, Majer Z, Neumann B, Stammler H, Sewald N, Yenesew A. "A xanthone and a phenylanthraquinone from the roots of Bulbine frutescens and the revision of six seco-anthraquinones into xanthones." Phytochemistry Letters. 2014;9:67-73.
2013
Endale M, Ekberg A, Alao JP, Akala HM, Ndakala A, Sunnerhagen P, Erdelyi M, Yenesew A. "Anthraquinones of the roots of Pentas micrantha." Molecules. 2013;18:311-321.
Abdissa N, Induli M, Akala HM, Heydenreich M, Midiwo JO, Ndakala A, Yenesew A. "Knipholone Cyclooxanthrone and an Anthroquinone Dimer with Antiplasmodial Activities from the Roots of Kniphofia Foliosa." Phytochemistry Letters . 2013;9(2):241-245.
2012
Endale M, Alao JP, Akala HM, Rono NK, Eyase FL, Solomon D, Ndakala A, Mbugua M, Walsh DS, Erdelyl M, Yenesew A. "Antiplasmodial Quinones from Pentas longiflora and Pentas lanceolata." Planta Medica . 2012;78(1):31-35.
2011
Ndakala AJ, Gessner RK, Gitari PW, October N, White KL, Hudson A, Fakorede F, Shackleford DM, Kaiser M, Yeates C, Charman SA, Chibale K. "Antimalarial Pyrido[1,2-a]benzimidazoles." Journal of Medicinal Chemistry. 2011;54:4581-4589.Website
2003
Taboada R, Ordonio GG, Ndakala AJ, Howell AR. "Directed Ring-Opening of 1,5-Dioxaspiro[3.2]hexanes: Selective Formation of 2,2-Disubstituted Oxetanes." Journal of Organic Chemistry. 2003;68:1480-1488. AbstractWebsite

In this retrospective study carried out covering the period, 1978-1991, 62 neonates were seen, diagnosed and treated for intestinal atresia which included: duodenal atresia and stenosis, small bowel atresia and atresia of large bowel. Locations of obstruction were duodenal in 17 patients, jejunal in 25 patients, jejuno-ileal in 5 and colon in two. Duodenal atresia was noted in 9 infants and duodenal stenosis due to annular pancreas, Ladd's bands with malrotation of bowel in 8. Associated anomalies which were observed were anorectal malformations in 2 and malrotation in 2 infants. Birth weights ranged from 1450 gm to 3000 gm. Prematurity was recorded in 11 infants. Diagnosis of intestinal atresia in our patients was made clinically and radiologically. Intestinal atresia in neonates was differentiated from other causes of obstruction such as Meconium Ileus, Hirschsprung's disease, neonatal volvulus, rectal atresia in anorectal malformations. Treatment of infants with intestinal atresia was surgical. Surgical techniques used depended on pathological findings. In 36 patients, complications such as functional obstructions with vomiting and failure to thrive, malabsorption, aspiration, bronchopneumonia, sepsis were observed. Overall mortality rate in our cases was 25 (41.9%) out of 62 patients.

Martinez I, Andrews AE, Emch JD, Ndakala AJ, Wang J, Howell AR. "Unusual, Strained Heterocycles: 3-Alkylidene-2-methyleneoxetanes from Morita-Baylis-Hillman-type Adducts." Organic Letters. 2003;68:399-402.
2002
Howell AR, Ndakala AJ. "The Preparation and the Biological Significance of Phytosphingosines." Current Organic Chemistry. 2002;6:365-391.
1999
Lwande W, Ndakala AJ, A H, Moreka L, Nyandat E, Ndungu M, Amiani H, Gitu PM, Malonza MM, Punyua DK. "Gynandropsis gynandra Essential Oil and Its Constituents as Tick (Rhipicephalus appendiculatus ) Repellents." Phytochemistry. 1999;50:401-405. AbstractWebsite

 
 
 
 

Dollinger LM, Ndakala AJ, Hashemzadeh M, Wang G, Wang Y, Martinez I, Arcari J, Galluzo DJ, Howell AR, Rheingold AL, Figuero JS. "Preparation and Properties of 2-Methyleneoxetanes." Journal of Organic Chemistry. 1999;64:7074-7080. AbstractWebsite

 
 
 
 

1998
Ndakala AJ, Howell AR. "The First General Synthesis of 1,5-Dioxaspiro[3.2]hexanes,"." Journal of Organic Chemistry 63 , 6098-6099.. 1998;63:6098-6099. AbstractWebsite

 
 
 
 

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