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Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment |
| Kennedy D. Nyongbela1,2, Fidele Ntie-Kang3, Thomas R. Hoye2, Simon M. N. Efange1 |
1. Pharmacochemistry Research Group, Department of Chemistry, University of Buea, P. O. Box 63, Buea, Cameroon;
2. Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, MN, USA;
3. Chemical and Bioactivity Information Centre, Department of Chemistry, University of Buea, P. O. Box 63, Buea, Cameroon |
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Abstract The antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1-6), isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is reported. The study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The in silico method employed a total of 46 descriptors, calculated using Schrödinger QikProp software. 18 of these molecular descriptors that are often used to predict DMPK profiles of drug-like molecules have been selected for discussion. In vitro experimental assessment of metabolic stability made use of human liver microsomes, which was used to correlate theoretical predictions with experimental findings. Overall, the test compounds have been found to have acceptable physicochemical properties and fall within the ranges associated with “drug-like” molecules. Moreover, the compounds exhibited minimal degradation in incubations with human liver microsomes. Although some of these compounds have been reported previously (1, 2, 4 and 5), this is the first report on their antiparasitic activities, as well as assessment of their DMPK profiles. These results have therefore provided a window for further development of this novel class of sesquiterpene molecules as potential antiparasitic drugs.
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| Keywords
Sesquiterpenes
Pharmacokinetics
Drug metabolism
Scleria striatinux
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| Fund:We are grateful for financial support from the International Cooperative Biodiversity Groups (ICBG),a program of the Fogarty International Centre of the National Institutes of Health (NIH),USA through grant (no TW00327) awarded to Professor S. M.N.Efange and Medicines for Malaria Venture (MMV),Geneva, Switzerland.The US Fulbright Council for International Exchange of Scholars (CIES) is acknowledged for grant to Kennedy D.Nyongbela to carry-out research at the University of Minnesota.We wish to thank M.Campbell and A.Powell from the Centre for Drug Candidate Optimisation (CDCO),Monash University for the DMPK data.Fidele Ntie-Kang is currently a Georg Forster fellow of the Alexander von Humboldt Foundation,Germany.We are equally grateful to Schrödinger Inc.for the academic license to use the QikProp software. |
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Issue Date: 06 February 2018
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