TY - GEN A1 - Nondo, Ramadhani Selemani Omari A1 - Moshi, Mainen Julius A1 - Erasto, Paul A1 - Masimba, Pax Jessey A1 - Machumi, Francis A1 - Kidukuli, Abdul Waziri A1 - Heydenreich, Matthias A1 - Zofou, Denis T1 - Anti-plasmodial activity of Norcaesalpin D and extracts of four medicinal plants used traditionally for treatment of malaria T2 - Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe N2 - Background: Malaria is an old life-threatening parasitic disease that is still affecting many people, mainly children living in sub-Saharan Africa. Availability of effective antimalarial drugs played a significant role in the treatment and control of malaria. However, recent information on the emergence of P. falciparum parasites resistant to one of the artemisinin-based combination therapies suggests the need for discovery of new drug molecules. Therefore, this study aimed to evaluate the antiplasmodial activity of extracts, fractions and isolated compound from medicinal plants traditionally used in the treatment of malaria in Tanzania. Methods: Dry powdered plant materials were extracted by cold macerations using different solvents. Norcaesalpin D was isolated by column chromatography from dichloromethane root extract of Caesalpinia bonducella and its structure was assigned based on the spectral data. Crude extracts, fractions and isolated compound were evaluated for antiplasmodial activity against chloroquine-sensitive P. falciparum (3D7), chloroquine-resistant P. falciparum (Dd2, K1) and artemisinin-resistant P. falciparum (IPC 5202 Battambang, IPC 4912 Mondolkiri) strains using the parasite lactate dehydrogenase assay. Results: The results indicated that extracts of Erythrina schliebenii, Holarrhena pubescens, Dissotis melleri and C. bonducella exhibited antiplasmodial activity against Dd2 parasites. Ethanolic root extract of E. schliebenii had an IC50 of 1.87 mu g/mL while methanolic and ethanolic root extracts of H. pubescens exhibited an IC50 = 2.05 mu g/mL and IC50 = 2.43 mu g/mL, respectively. Fractions from H. pubescens and C. bonducella roots were found to be highly active against K1, Dd2 and artemisinin-resistant parasites. Norcaesalpin D from C. bonducella root extract was active with IC50 of 0.98, 1.85 and 2.13 mu g/mL against 3D7, Dd2 and IPC 4912-Mondolkiri parasites, respectively. Conclusions: Antiplasmodial activity of norcaesalpin D and extracts of E. schliebenii, H. pubescens, D. melleri and C. bonducella reported in this study requires further attention for the discovery of antimalarial lead compounds for future drug development. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 707 KW - antiplasmodial KW - norcaesalpin D KW - E. schliebenii KW - H. pubescens KW - D. melleri KW - C. bonducella Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-428325 SN - 1866-8372 IS - 707 ER - TY - JOUR A1 - Chepkirui, Carolyne A1 - Ochieng, Purity J. A1 - Sarkar, Biswajyoti A1 - Hussain, Aabid A1 - Pal, Chiranjib A1 - Yang, Li Jun A1 - Coghi, Paolo A1 - Akala, Hoseah M. A1 - Derese, Solomon A1 - Ndakala, Albert A1 - Heydenreich, Matthias A1 - Wong, Vincent K. W. A1 - Erdelyi, Mate A1 - Yenesew, Abiy T1 - Antiplasmodial and antileishmanial flavonoids from Mundulea sericea JF - Fitoterapia N2 - 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 mu M against chloroquine-resistant W2, and 6.6 mu M 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 mu M, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC50 4.9 mu M) and HePG2 (IC50 10.8 mu M) human cell lines. All the other compounds showed low cytotoxicity (IC50 > 30 mu M) against human lung adenocarcinoma cells (A549), human liver cancer cells (HepG2), lung/bronchus cells (epithelial virus transformed) (BEAS-2B) and immortal human hepatocytes (LO2) KW - Mundulea sericea KW - leguminosae KW - flavanonol KW - flavonol KW - antiplasmodial KW - antileishmanial KW - cytotoxicity Y1 - 2020 U6 - https://doi.org/10.1016/j.fitote.2020.104796 SN - 0367-326X SN - 1873-6971 VL - 149 PB - Elsevier CY - Amsterdam 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 - Atilaw, Yoseph A1 - Duffy, Sandra A1 - Heydenreich, Matthias A1 - Muiva-Mutisya, Lois A1 - Avery, Vicky M. A1 - Erdelyi, Mate A1 - Yenesew, Abiy T1 - Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata JF - Molecules N2 - In our search for new antiplasmodial agents, the CH2Cl2/CH3OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL concentration. From this extract three new chalconoids, E-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (1, aequichalcone A), Z-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (2, aequichalcone B), 4-ethoxy-3-hydroxypraecansone B (3, aequichalcone C) and a new pterocarpene, 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (4), along with seven known compounds were isolated. The purified compounds were characterized by NMR spectroscopic and mass spectrometric analyses. Compound 1 slowly converts into 2 in solution, and thus the latter may have been enriched, or formed, during the extraction and separation process. The isomeric compounds 1 and 2 were both observed in the crude extract. Some of the isolated constituents showed good to moderate antiplasmodial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum. KW - Tephrosia aequilata KW - chalcone KW - retrochalcone KW - aequichalcone A KW - aequichalcone B KW - aequichalcone C KW - pterocarpene KW - antiplasmodial Y1 - 2017 U6 - https://doi.org/10.3390/molecules22020318 SN - 1420-3049 VL - 22 IS - 2 PB - MDPI CY - Basel ER -