Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

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. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13659-017-0125-y) contains supplementary material, which is available to authorized users.