TY - JOUR A1 - Adem, Fozia A. A1 - Kuete, Victor A1 - Mbaveng, Armelle T. A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Ndakala, Albert A1 - Irungu, Beatrice A1 - Yenesew, Abiy A1 - Efferth, Thomas T1 - Cytotoxic flavonoids from two Lonchocarpus species JF - Natural Product Research N2 - 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 μM were observed for the isoflavones 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone and durmillone against leukemia CCRF-CEM cells; for the chalcone, 4-hydroxylonchocarpin and durmillone against its resistant counterpart CEM/ADR5000 cells; as well as for durmillone against the resistant breast adenocarcinoma MDA-MB231/BCRP cells and resistant gliobastoma U87MG.ΔEGFR cells. KW - Lonchocarpus bussei KW - Lonchocarpus eriocalyx KW - Leguminosae KW - isoflavone KW - pterocarpan KW - cytotoxicity Y1 - 2019 U6 - https://doi.org/10.1080/14786419.2018.1462179 SN - 1478-6419 SN - 1478-6427 VL - 33 IS - 18 SP - 2609 EP - 2617 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Adem, Fozia A. A1 - Kuete, Victor A1 - Mbaveng, Armelle T. A1 - Heydenreich, Matthias A1 - Ndakala, Albert A1 - Irungu, Beatrice A1 - Efferth, Thomas A1 - Yenesew, Abiy T1 - Cytotoxic benzylbenzofuran derivatives from Dorstenia kameruniana JF - Fitoterapia N2 - 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 mu M and 5.16 mu M, respectively) against CCRF-CEM leukemia cells. Compound 5 also showed cytotoxicity against 7 sensitive or drug-resistant solid tumor cell lines (breast carcinoma, colon carcinoma, glioblastoma), with IC50 below 50 mu M, whilst 4 showed selective activity. KW - Dorstenia kameruniana KW - Moraceae KW - Benzylbenzofuran KW - Furanocoumarin KW - Chalcone KW - Cytotoxicity Y1 - 2018 U6 - https://doi.org/10.1016/j.fitote.2018.04.019 SN - 0367-326X SN - 1873-6971 VL - 128 SP - 26 EP - 30 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Adem, Fozia A. A1 - Mbaveng, Armelle T. A1 - Kuete, Victor A1 - Heydenreich, Matthias A1 - Ndakala, Albert A1 - Irungu, Beatrice A1 - Yenesew, Abiy A1 - Efferth, Thomas T1 - Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer JF - Phytomedicine : international journal of phytotherapy and phytopharmacology N2 - 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. Methods: The cytotoxicity of compounds was determined based on the resazurin reduction assay. Caspases activation was evaluated using the caspase-Glo assay. Flow cytometry was used to analyze the cell cycle (propodium iodide (PI) staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). CCRF-CEM leukemia cells were used as model cells for mechanistic studies. Results: Compounds 1, 2 and 4 displayed IC50 values below 20 mu M towards CCRF-CEM and CEM/ADR5000 leukemia cells, and were further tested towards a panel of 7 carcinoma cells. The IC50 values of the compounds against carcinoma cells varied from 16.90 mu M (in resistant U87MG.Delta EGFR glioblastoma cells) to 48.67 mu M (against HepG2 hepatocarcinoma cells) for 1, from 7.85 mu M (in U87MG.Delta EGFR cells) to 14.44 mu M (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2, from 4.96 mu M (towards U87MG.Delta EGFRcells) to 7.76 mu M (against MDA-MB231/BCRP cells) for 4, and from 0.07 mu M (against MDA-MB231 cells) to 2.15 mu M (against HepG2 cells) for doxorubicin. Compounds 2 and 4 induced apoptosis in CCRF-CEM cells mediated by MMP alteration and increased ROS production. Conclusion: The present report indicates that isoflavones and biflavonoids from Ormocarpum kirkii are cytotoxic compounds with the potential of being exploited in cancer chemotherapy. Compounds 2 and 4 deserve further studies to develop new anticancer drugs to fight sensitive and resistant cancer cell lines. KW - Apoptosis KW - Cancer KW - Ormocarpum kirkii KW - Isoflavone KW - Biflavonoid KW - Multi-drug resistance Y1 - 2019 U6 - https://doi.org/10.1016/j.phymed.2019.152853 SN - 0944-7113 SN - 1618-095X VL - 58 PB - Elsevier CY - München ER - TY - JOUR A1 - Irungu, Beatrice N. A1 - Adipo, Nicholas A1 - Orwa, Jennifer A. A1 - Kimani, Francis A1 - Heydenreich, Matthias A1 - Midiwo, Jacob O. A1 - Bjoremark, Per Martin A1 - Hakansson, Mikael A1 - Yenesew, Abiy A1 - Erdelyi, Mate T1 - Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica JF - Journal of ethnopharmacology : an interdisciplinary journal devoted to bioscientific research on indigenous drugs N2 - 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. Materials and methods: From the stem bark of T. robusta six compounds, and from various parts of T nilotica eleven compounds were isolated by the use of a combination of chromatographic techniques. The structures of the isolated compounds were elucidated using NMR and MS, whilst the relative configuration of one of the isolated compounds, toonapubesin F, was established by X-ray crystallography. The antiplasmodial activities of the crude extracts and the isolated constituents against the D6 and W2 strains of Plasmodium falciparum were determined using the semiautomated micro dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-H-3, where G is guanine) hypoxanthine into the malaria parasite. The cytotoxicity of the crude extracts and their isolated constituents was evaluated against the mammalian cell lines African monkey kidney (vero), mouse breast cancer (4T1) and human larynx carcinoma (HEp2). Results: The extracts showed good to moderate antiplasmodial activities, where the extract of the stem bark of T. robusta was also cytotoxic against the 4T1 and the HEp2 cells (IC50 < 10 mu g/ml). The compounds isolated from these extracts were characterized as limonoids, protolimonoids and phytosterol glucosides. These compounds showed good to moderate activities with the most active one being azadironolide, IC50 2.4 +/- 0.03 mu M and 1.1 +/- 0.01 mu M against the D6 and W2 strains of Plasmodium falciparum, respectively; all other compounds possessed IC50 14.4-40.5 mu M. None of the compounds showed significant cytotoxicity against vero cells, yet four of them were toxic against the 4T1 and HEp2 cancer cell lines with piscidinol A having IC50 8.0 +/- 0.03 and 8.4 +/- 0.01 mu M against the 4T1 and HEp2 cells, respectively. Diacetylation of piscidinol A resulted in reduced cytotoxicity. Conclusion: From the medicinal plants T. robusta and T. nilotica, twelve compounds were isolated and characterized; two of the isolated compounds, namely 11-epi-toonacilin and azadironolide showed good antiplasmodial activity with the highest selectivity indices. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. KW - Turraea robusta KW - Turraea nilotica KW - Antiplasmodial activity KW - Cytotoxicity KW - Limonoid KW - Toonapubesins F KW - Toonacilin KW - Azadironolide Y1 - 2015 U6 - https://doi.org/10.1016/j.jep.2015.08.039 SN - 0378-8741 VL - 174 SP - 419 EP - 425 PB - Elsevier CY - Clare ER - TY - JOUR A1 - Muiva-Mutisya, Lois M. A1 - Atilaw, Yoseph A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Akala, Hoseah M. A1 - Cheruiyot, Agnes C. A1 - Brown, Matthew L. A1 - Irungu, Beatrice A1 - Okalebo, Faith A. A1 - Derese, Solomon A1 - Mutai, Charles A1 - Yenesew, Abiy T1 - Antiplasmodial prenylated flavanonols from Tephrosia subtriflora JF - Natural Product Research N2 - 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 Plasmodiumfalciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC50 values 1.4-4.6M without significant cytotoxicity against Vero and HEp2 cell lines (IC50>100M). The new compound (1) showed weak antiplasmodial activity, IC50 12.5-24.2M, but also showed selective anticancer activity against HEp2 cell line (CC50 16.9M). [GRAPHICS] . KW - Tephrosia subtriflora KW - Leguminosae KW - prenylated flavanonol KW - subtriflavanonol KW - antiplasmodial KW - cytotoxicity Y1 - 2018 U6 - https://doi.org/10.1080/14786419.2017.1353510 SN - 1478-6419 SN - 1478-6427 VL - 32 IS - 12 SP - 1407 EP - 1414 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Muthaura, Charles N. A1 - Keriko, Joseph M. A1 - Mutai, Charles A1 - Yenesew, Abiy A1 - Heydenreich, Matthias A1 - Atilaw, Yoseph A1 - Gathirwa, Jeremiah W. A1 - Irungu, Beatrice N. A1 - Derese, Solomon T1 - Antiplasmodial, cytotoxicity and phytochemical constituents of four maytenus species used in traditional medicine in Kenya JF - The natural products journal N2 - 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 as 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 promising antiplasmodial activity with IC50, 3.63 and 3.95 ng/ml against chloroquine sensitive (D6) and resistant (W2) P. falciparum, respectively and moderate cytotoxicity (CC50, 37.5 ng/ml) against Vero E6 cells. The other compounds showed weak antiplasmodial (IC50 > 1.93 mu g/ml) and cytotoxic (CC50 > 39.52 mu g/ml) activities against P. falciparum and Vero E6 cells, respectively. Conclusion: (20 alpha)-3-hydroxy-2-oxo-24-nor-friedela-1(10),3,5,7-tetraen-carboxylic acid-(29)-methyl-ester (pristimerin) (1) was the most active marker and lead compound that warrants further investigation as a template for the development of new antimalarial drugs. Pristimerin is reported for the first time in M. putterlickioides. 3-Hydroxyolean-12-en-28-oic acid (oleanolic acid) (5), stigmast-5-en-3-ol (beta-sitosterol) (6), 3-oxo-28-friedelanoic acid (7), olean-12-en-3-ol (beta-amyrin) (8), lup-20(29)-en-3-ol (lupeol) (9) and lup-20(29)-en-3-one (lupenone) (10) are reported for the first time in M. undata. KW - Antimalarial plants KW - antiplasmodial KW - cytotoxicity KW - marker compound KW - Maytenus spp. KW - phytomedicine KW - pristimerin Y1 - 2017 U6 - https://doi.org/10.2174/2210315507666161206144050 SN - 2210-3155 SN - 2210-3163 VL - 7 IS - 2 SP - 144 EP - 152 PB - Bentham Science Publ. CY - Sharjah ER - TY - JOUR A1 - Yaouba, Souaibou A1 - Koch, Andreas A1 - Guantai, Eric M. A1 - Derese, Solomon A1 - Irungu, Beatrice A1 - Heydenreich, Matthias A1 - Yenesew, Abiy T1 - Alkenyl cyclohexanone derivatives from Lannea rivae and Lannea schweinfurthii JF - Phytochemistry letters / Phytochemical Society of Europe N2 - 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. KW - Lannea rivae KW - Lannea schweinfurthii KW - Alkenyl cyclohexenone KW - Alkenyl cyclohexanone KW - Anti-inflammatory KW - Cytotoxicity KW - Antimicrobial Y1 - 2017 U6 - https://doi.org/10.1016/j.phytol.2017.12.001 SN - 1874-3900 SN - 1876-7486 VL - 23 SP - 141 EP - 148 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Yenesew, Abiy A1 - Irungu, Beatrice A1 - Derese, Solomon A1 - Midiwo, Jacob O. A1 - Heydenreich, Matthias A1 - Peter, Martin G. T1 - Two prenylated flavonoids from the stem bark of Erythrina burttii N2 - From the stem bark of Erythrina burttii, a new isoflavone, 5,2',4'-trihydroxy-7-methoxy-6-(3- methylbut-2-enyl)isoflavone (trivial name, 7-O-methylluteone) and a new flavanone, 5,7-dihydroxy-4'-methoxy- 3'-(3-methylbutadienyl)-5'-(3-methylbut-2-enyl)flavanone (trivial name, burttinonedehydrate) along with three known isoflavonoids (8-prenylluteone, 3-O-methylcalopocarpin and genistein) were isolated. The structures were detd. on the basis of spectroscopic evidence. Y1 - 2003 ER -