| PROF. YENESEW ABIY

Natural products and Drug development

Bio

PROF. YENESEW ABIY

I am a Professor of Chemistry at the University of Nairobi, Kenya. I have an extensive experience in teaching of Organic Chemistry and conducting research in the field of Natural Products Chemistry. For the last thirty years, I have been involved in the investigation of Eastern African plants for bioactive natural products. This has resulted in the publication of 90 articles in peer reviewed journals (h-index of 30, H-10 index of 77, Citations 2453 in Google Scholar, as of 13th Jan 2020). I have also co-authored three books on medicinal plants of East Africa.

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Publications

2021

Buyinza, D, Derese S, Ndakala A, Heydenreich M, Yenesew A, Koch A, Oriko R. 2021. A coumestan and a coumaronochromone from Millettia lasiantha. Biochemical Systematics and Ecology. 97:104277. AbstractView Website

Description
The manuscript describes the phytochemical investigation of the roots, leaves and stem bark of Millettia lasiantha resulting in the isolation of twelve compounds including two new isomeric isoflavones lascoumestan and lascoumaronochromone. The structures of the new compounds were determined using different spectroscopic techniques.

Ochora, DO, Kakudidi E, Namukobe J, Heydenreich M, Coghi P, Yang LJ, Mwakio EW, Andagalu B, Roth A, Akala HM, Wong VKW, Yenesew A. 2021. A new benzophenone, and the antiplasmodial activities of the constituents of Securidaca longipedunculata fresen (Polygalaceae). Natural Product Research. :1-9. AbstractView Website

Description
Extracts from Securidaca longipedunculata showed antiplasmodial activities against reference clones and clinical isolates using SYBR Green I method. A new benzophenone, 2,3,4,5-tetramethoxybenzophenone (1) was isolated and characterized along with seven known compounds: 4-hydroxy-2,3-dimethoxybenzophenone (2); 3-hydroxy-5-methoxybiphenyl (3), methyl-2-hydroxy-6-methoxybenzoate (4), benzyl-2-hydroxy-6-methoxybenzoate (5), 2-hydroxy-6-methoxybenzoic acid (6), 2,4,5-trimethoxybenzophenone (7) and 2-methoxy-3,4-methylenedioxybenzophenone (8). Compounds 1 and 2 showed ex vivo antiplasmodial activities (IC50 28.8 μM and 18.6 μM, respectively); while 5 and 8 showed in vivo activities (IC50 19.7 μM and 14.5 μM, respectively) against D6 strain. In a cytotoxicity assay, all the extracts (with an exception of the MeOH extract of the leaves) and pure compounds were not toxic to the …

Chepkirui, C, Ochieng PJ, Sarkar B, Hussain A, Pal C, Yang LJ, Coghi P, Akala HM, Derese S, Ndakala A, Heydenreich M, Wong VKW, Erdélyi Máté, Yenesew A. 2021. Antiplasmodial and antileishmanial flavonoids from Mundulea sericea. Fitoterapia. 149:104796. AbstractView Website

Description
Five known compounds (1–5) were isolated from the extract of Mundulea sericea leaves. Similar investigation of the roots of this plant afforded an additional three known compounds (6–8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC50 of 2.0 μM against chloroquine-resistant W2, and 6.6 μM against the chloroquine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishmanial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC50 values of 9.0 and 5.0 μM, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC50 4.9 μM) and HePG2 (IC50 10.8 μM …

Omosa, LK, Mbogo GM, Korir E, Omole R, Ean-JeongSeo, Yenesew A, Heydenreich M, Midiwo JO, Efferth T. 2021. Cytotoxicity of fagaramide derivative and canthin-6-one from Zanthoxylum (Rutaceae) species against multidrug resistant leukemia cells. Natural product research. 35(4):579-586. AbstractView Website

Description
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 …

Andima, M, Ndakala A, Derese S, Biswajyoti S, Hussain A, Yang LJ, Akoth OE, Coghi P, Pal C, Heydenreich M, Wong VK-W, Yenesew A. 2021. Antileishmanial and cytotoxic activity of secondary metabolites from Taberneamontana ventricosa and two aloe species. Natural Product Research. :1-5. AbstractNatural Product Research

Description
In this study, the antileishmanial and cytotoxic activities of secondary metabolites isolated from Tabernaemontana ventricosa Hochst. ex A. DC., Aloe tororoana Reynolds, and Aloe schweinfurthii var. labworana Reynolds were investigated. Overall, nineteen known compounds were isolated from the three plant species. The compounds were characterized based on their spectroscopic data. Voacristine and aloenin were the most active compounds against promastigotes of antimony-sensitive Leishmania donovani (IC50 11 ± 5.2 μM and 26 ± 6.5 µM, respectively) with low toxicity against RAW264.7, murine monocyte/macrophage-like cells. The in silico docking evaluation and in vitro NO generation assay also substantially support the antileishmanial effects of these compounds. In a cytotoxicity assay against cancer and normal cell lines, ursolic acid highly inhibited proliferation of lung cancer cells, A549 …

2020

Chalo, DM, Kakudidi E, Origa-Oryem H, Namukobe J, Franke K, Yenesew A, Wessjohann LA. 2020. Chemical constituents of the roots of Ormocarpum sennoides subsp. zanzibaricum. Biochemical Systematics and Ecology. 93:104142. AbstractBiochemical Systematics and Ecology

Description
Phytochemical investigation of the roots of O. sennoides subsp. zanzibaricum Brenan & J.B. Gillett resulted in the isolation of three biflavonoids (trime-chamaejasmin, (+)- chamaejasmin, (+)-liquiritigeninyl-(I-3,II-3)-naringenin), one bi-4-phenyldihydrocoumarin (diphysin), one isoflavan (glabridin), one triterpenoid (3-O-acetyloleanoic acid) and a phytosterol (β-sitosterol). Compounds were identified by detailed MS, 1D and 2D NMR spectroscopic analyses. Their absolute configurations were elucidated based on ECD spectra. The previously undescribed trime-chamaejasmin represents a bis-epi-chamaejasmenin C diastereomer. The chemophenetic significance is discussed in detail. The results contribute to the phytochemical characterization of the genus Ormocarpum and suggest a close chemophenetic relationship with other genera within the subfamily Papilionoideae. Furthermore, this report provides baseline …

Chepkirui, C, Ochieng PJ, Sarkar B, Hussain A, Pal C, Yang LJ, Coghi P, Akala HM, Derese S, Ndakala A, Heydenreich M, Wong VKW, Erdélyi Máté, Yenesew A. 2020. Antiplasmodial and antileishmanial flavonoids from Mundulea sericea. Fitoterapia. 149:104796. AbstractFitoterapia

Abstract
Five known compounds (1–5) were isolated from the extract of Mundulea sericea leaves. Similar investigation of the roots of this plant afforded an additional three known compounds (6–8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC50 of 2.0 μM against chloroquine-resistant W2, and 6.6 μM against the chloroquine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishmanial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC50 values of 9.0 and 5.0 μM, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC50 4.9 μM) and HePG2 (IC50 10.8 μM) human cell lines. All the other compounds showed low cytotoxicity (IC50 > 30 μM) against human lung adenocarcinoma cells (A549), human liver cancer cells (HepG2), lung/bronchus cells (epithelial virus transformed) (BEAS-2B) and immortal human hepatocytes (LO2)

Graphical abstract
Unlabelled Image

Atilaw, Y, Muiva-Mutisya L, Bogaerts J, Duffy S, Valkonen A, Heydenreich M, Avery VM, Rissanen K, Erdélyi M, Yenesew A. 2020. Prenylated Flavonoids from the Roots of Tephrosia rhodesica. Journal of natural products. 83(8):2390-2398. AbstractJournal of Natural Products

Description
Five new compounds—rhodimer (1), rhodiflavan A (2), rhodiflavan B (3), rhodiflavan C (4), and rhodacarpin (5)—along with 16 known secondary metabolites, were isolated from the CH2Cl2–CH3OH (1:1) extract of the roots of Tephrosia rhodesica. They were identified by NMR spectroscopic, mass spectrometric, X-ray crystallographic, and ECD spectroscopic analyses. The crude extract and the isolated compounds 2–5, 9, 15, and 21 showed activity (100% at 10 μg and IC50 = 5–15 μM) against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.

Kaigongi, MM, Lukhoba CW, Yaouba S, Makunga NP, Githiomi J, Yenesew A. 2020. In Vitro Antimicrobial and Antiproliferative Activities of the Root Bark Extract and Isolated Chemical Constituents of Zanthoxylum paracanthum Kokwaro (Rutaceae). Plants. 9(7):920. AbstractPlants

Description
Zanthoxylum paracanthum Kokwaro (Rutaceae) is an endemic Kenyan and Tanzanian plant used in folk medicine by local populations. Although other Zanthoxylum species have been studied, only Z. paracantum stem extracts have been profiled, even though the roots are also used as herbal remedies. As root extracts may be another source of pharmaceutical compounds, the CH 2 Cl 2/MeOH (1: 1) root bark extract was studied in this report. Eight root bark compounds were isolated and their structural identities were confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR)(using COSY, HSQC, NOESY and HMBC) analyses. The structural identities were determined as follows: the fatty acid—myristic acid (1); the sterol—stigmasterol (2); the lignan—sesamin (3); two β-carboline alkaloids—10-methoxycanthin-6-one (6) and canthin-6-one (7); and three phenanthridine alkaloids—8-acetonyldihydrochelerythrine (4), arnottianamide (5) and 8-oxochelerythrine (8). Some of these compounds were identified in the species for the first time. These compounds and the extract were then tested in vitro against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213) and Candida albicans (ATCC 10231) before tests for antiproliferative activity against the human breast cancer (HCC 1395), human prostate cancer (DU 145) and normal (Vero E6) cell lines were conducted. Minimum inhibition concentration values of 3.91, 1.95, 0.98 and 7.81 µg/mL against MRSA, S. aureus, E. coli and C. albicans, respectively, were recorded. Among the isolates, canthin-6-one was the …

Kaigongi, MM, Lukhoba CW, Taylor M, Yenesew A, Makunga NP. 2020. LC-MS-Based Metabolomics for the Chemosystematics of Kenyan Dodonaea viscosa Jacq (Sapindaceae) Populations. Molecules. 25(18):4130. AbstractMolecules

Description
Dodonaea viscosa Jacq (Sapindaceae) is a medicinal plant with a worldwide distribution. The species has undergone enormous taxonomic changes which caused confusion amongst plant users. In Kenya, for example, two varieties are known to exist based on morphology, ie, D. viscosa var. viscosa along the coast, and D. viscosa var. angustifolia in the Kenyan inland. These two taxa are recognized as distinct species in some reports. This prompted us to apply metabolomics to understand the relationship among naturally occurring populations of D. viscosa in Kenya, and to identify compounds that can assist in taxonomic delineation of the different varieties of D. viscosa from different parts of Kenya. The phytochemical variability of Kenyan D. viscosa var. angustifolia populations collected from four different geographical regions (Nanyuki, Machakos, Nairobi, and Narok) and one coastal D. viscosa var. viscosa (the Gazi) were analyzed by LC-MS using a metabolomics-driven approach. Four known compounds, two diterpenoids (dodonic acid (1), hautriwaic acid lactone (3), and two flavonoids (5, 7, 4′, 5′-tetrahydroxy-3, 6, 2′-trimethoxyflavone (2) and catechin (4)) were isolated and purified from the Gazi coastal collection. The presence of these compounds and their relative abundance in other populations was determined by LC-MS analyses. Multivariate statistical analyses of LC-MS data was used for the visualization of the patterns of variation and identification of additional compounds. Eleven discriminant compounds responsible for separating chemometric clusters were tentatively identified. In an antimicrobial assay, hautriwaic acid …

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

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

2019

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

Abstract

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).
Keywords: Millettia dura, Leguminosae, isoflavone, cytotoxicity.

Kennedy, O, Abiy Y, Ramni J, Andrew S, Keith S. 2019. A simple field based method for rapid wood density estimation for selected tree species in Western Kenya. Scientific African. 5:e00149.

Fozia, AA, Victor K, Armelle MT, Matthias H, Andreas K, Albert N, Beatrice I, Abiy Y, Thomas E. 2019. Cytotoxic flavonoids from two Lonchocarpus species. Natural Product Research. 33(18):2609-2617.

Macharia, FK, Mwangi PW, Yenesew A, Bukachi F, Nyaga NM, Wafula DK. 2019. Hepatoprotective effects of Erythrina abyssinica Lam Ex Dc against Non Alcoholic Fatty Liver Disease in Sprague Dawley Rats. BioRxiv. :577-607. Abstract

Non-alcoholic fatty liver disease (NFLD) is the hepatic manifestation of the metabolic syndrome recognized as the most prevalent chronic liver disease across all age groups. NFLD is strongly associated with obesity, insulin resistance, hypertension and dyslipidemia. Extensive research efforts are geared, through pharmacological approach, towards preventing or reversing this. Erythrina abyssinica Lam ex DC is an indigenous tree used widely used in traditional medicine, including for the treatment of liver related diseases, and has been shown to possess hypoglycemic, anti-oxidant, antimicrobial and anti-plasmodia effects. The present study is aimed at establishing the effects of E. abyssinica on the development of Non-alcoholic fatty liver disease induced by a high-fat and high-sugar diet in rats, in-vivo model. Methods: Forty rats (40) were randomly divided into five groups: positive control (pioglitazone), Negative control (high fat/high sugar diet), low test dose (200 mg/kg), high test dose (400 mg/kg) and normal group (standard chow pellets and fresh water). The inhibitory effect of the stem bark extract of E. abyssinica on the development of NAFLD was evaluated by chronic administration the herb extracts to rats on a high-fat/high-sugar diet. Biochemical indices of hepatic function including serum lipid profile, serum aspartate transaminase and alanine transaminase levels were then determined. Histological analysis of liver samples was carried out to quantify the degree of steato-hepatitis. Liver weights were taken and used to determine the hepatic index. The data was analyzed using one-way ANOVA, and Tukey9s post-hoc tests

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.

Adem, FA, Mbaveng AT, Kuete V, Heydenreich M, Ndakala A, Irungu B, Yenesew A, Efferth T. 2019. Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer. Phytomedicine. 58:152-853. Abstract

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.

2018

Yaouba, S, Koch A, Guantai EM, Derese S, Irungu B, Heydenreich M, Yenesew A. 2018. Alkenyl cyclohexanone derivatives from Lannea rivae and Lannea schweinfurthii. Phytochemistry letters. 23:141-148. AbstractJornal article

Abstract
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.

Graphical abstract

Muiva-Mutisya, LM, Atilaw Y, Heydenreich M, Koch A, Akala HM, Cheruiyot AC, Brown ML, Irungu B, Okalebo FA, Derese S, Mutai C, Yenesew A. 2018. Antiplasmodial prenylated flavanonols from Tephrosia subtriflora. Natural product research. 32(12):1407-1414. AbstractJournal article

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 (CC50 16.9 μM).

Keywords: Tephrosia subtriflora, Leguminosae, prenylated flavanonol, subtriflavanonol, antiplasmodial, cytotoxicity

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

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

Yaouba, S, Valkonen A, Coghi P, Gao J, Guantai EM, Derese S, Wong VKW, Erdélyi Máté, Yenesew A. 2018. Crystal Structures and Cytotoxicity of ent-Kaurane-Type Diterpenoids from Two Aspilia Species. Molecules. 23(12):31-99. 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.

2017

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):1934578X1701200521. AbstractJournal article

Abstract
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.

Keywords Diterpenes, Kauranes, Trachylobanes, Psiadia punctulata, Structure-activity relationship, Lipophilicity, Computational study

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. AbstractJournal article

Description
Background:
In Kenya, several species of the genus Maytenus are used in traditional medicine to treat many diseases including malaria. In this study, phytochemical constituents and extracts of Maytenus undata, M. putterlickioides, M. senegalensis and M. heterophylla were evaluated to determine compound/s responsible for antimalarial activity.
Objective:
To isolate antiplasmodial compounds from these plant species which could be used marker compounds in the standardization of their extracts as a phytomedicine for malaria.
Methods:
Constituents were isolated through activity-guided fractionation of the MeOH/CHCl3 (1:1) extracts and in vitro inhibition of Plasmodium falciparum. Cytotoxicity was evaluated using Vero cells and the compounds were elucidated on the basis of NMR spectroscopy.
Results:
Fractionation of the extracts resulted in the isolation of ten known compounds. Compound 1 showed …
Total citations
Cited by 1
2018
Scholar articles
Antiplasmodial, Cytotoxicity and Phytochemical Constituents of Four Maytenus Species Used in Traditional Medicine in Kenya
CN Muthaura, JM Keriko, C Mutai, A Yenesew… - The Natural Products Journal, 2017
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Atilaw, Y, Akala HM, Coghi P, Wong VKW, Erdélyi M, Yenesew A. 2017. ). Four flavones with modified prenyl groups from the stem of Tephroisa purpurea subsp. Leptostachya. paper_88_atilaw_et_al_molecules-sept_2017.pdf

Marco, M, Deyou T, Heydenreich M, Koch A, Erdélyi M, Yenesew A. 2017. Two pterocarpans from Millettia dura and Millettia micans. paper_86_marco_et_al-2017.pdf

Muiva-Mutisya, LM, Heydenreich M, Koch A, Akala HM, Yenesew A. 2017. Antiplasmodial prenylated flavanonols from Tephrosia subtriflora. paper_87_muiva-mutisya_et_al-2017.pdfpaper_87a_muiva-mutisya_et_al-si-2017.pdf

Deyou, T, Marco M, Heydenreich M, Yenesew A, Erdélyi M. 2017. ) Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp. teitensis. paper_85_deyou_et_al_jnp-2017.pdf

Atilaw, Y, Heydenreich M, Erdélyi Máté, Duffy S, Yenesew A. 2017. Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata. paper_84_atilaw_et_al_molecules-22-00318.pdf

A new triterpenoid, 3-oxo-12β-hydroxy-oleanan-28,13β-olide (1), and six known
triterpenoids 2–7 were isolated from the root bark of Ekebergia capensis, an African
medicinal plant. A limonoid 8 and two glycoflavonoids 9–10 were found in its leaves. The
metabolites were identified by NMR and MS analyses, and their cytotoxicity was evaluated
against the mammalian African monkey kidney (vero), mouse breast cancer (4T1), human
larynx carcinoma (HEp2) and human breast cancer (MDA-MB-231) cell lines. Out of the
isolates, oleanonic acid (2) showed the highest cytotoxicity, i.e., IC50’s of 1.4 and 13.3 μM
against the HEp2 and 4T1 cells, respectively. Motivated by the higher cytotoxicity of the
crude bark extract as compared to the isolates, the interactions of oleanonic acid (2) with five triterpenoids 3–7 were evaluated on vero cells. In an antiplasmodial assay, seven
of the metabolites were observed to possess moderate activity against the D6 and W2
strains of P. falciparum (IC50 27.1–97.1 μM), however with a low selectivity index
(IC50(vero)/IC50(P. falciparum-D6) < 10). The observed moderate antiplasmodial activity
may be due to general cytotoxicity of the isolated triterpenoids.

Keywords: Ekebergia capensis; tritepenoid; antiplasmodial; cytotoxicity; Vero; 4T1;
HEp2; MDA-MB-231; 3-oxo-12β-hydroxy-oleanan-28,13β-olide

Yenesew, A, Muiva-Mutisya L, Macharia B, Heydenreich M, Andreas Koch, Hoseah M. Akala SDLOK. 2014. 6α-Hydroxy-α-toxicarol and (+)-Tephrodin with antiplasmodial activities from Tephrosia species. Phytochemistry Letters . Abstractpaper_75_muiva_et_al_phyto_2014.pdf

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.

Yenesew, A, Gumula I, Erdélyi M, Patrick. A, J Isaiah Omolo Ndiege PS, Omolo, N, Sunnerhagen P. 2014. Cytotoxic and Antioxidant Flemingins G-P from the Leaves of Flemingia grahamiana. Journal of Natural Products . Abstractpaper_76_ivan_et_al_jnp_2014_77_2060_2067.pdf

The known flemingins A-C (1-3) and nine new chalcones, named flemingins G-O (4-12), along with deoxyhomoflemingin (13) and emodin (14) were isolated from a leaf extract of Flemingia grahamiana. The isolated chalcones were found to have a geranyl substituent modified into a chromene ring possessing a residual chain, as shown by spectroscopic methods. The leaf extract showed an IC50 value of 5.9 μg/mL in a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. The chalcones flemingins A, B, C, G, and H were active in the DPPH radical scavenging assay (ED50 4.4-8.9 μM), while flemingins A and C showed cytotoxicity against MCF-7 human breast cancer cells (IC50 8.9 and 7.6 μM, respectively).

PROF. YENESEW ABIY

Ph.D. (1997) and MSc. (1992) in Chemistry, University of Nairobi. BSc.(1984) in Chemistry, Addis Ababa University, Ethiopia

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