Designing new antimalarial hits from African medicinal plants at the University of Buea (Cameroon); Part I: Isolation, in vitro activity, in silico “drug-likeness” and Pharmacokinetic profiles

tested with long-acting prescription antimalarials, lumefantrine and piperaquine. Methods & Materials: LC-ESI-MS/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99-411 and of piperaquine and 99-411 combinations. The interaction studies were performed in rats using these validated methods. Results: The total systemic exposure of 99-411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99-411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99-411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99-411, an in situ permeability study was performed by coperfusing lumefantrine and 99-411. In presence of lumefantrine, the absorption of 99-411 was significantly increased by 1.37 times than when given alone. Conclusion: Short-acting CDRI candidate antimalarial trioxane derivative, 99-411, was found to be pharmacokinetically compatible with long-acting prescription antimalarials, lumefantrine.