Alkaloids with Anti-Onchocercal Activity from Voacanga africana Stapf (Apocynaceae): Identification and Molecular Modeling

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A ( ), along with eight known compounds-voacangine ( ), voacristine ( ), coronaridine ( ), tabernanthine ( ), iboxygaine ( ), voacamine ( ), voacorine ( ) and conoduramine ( )-were isolated from the stem bark of . The structures of the compounds were determined by comprehensive spectroscopic analyses. Compounds , , , , , and were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of , in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC values of the isolates are 2.49-5.49 µM for microfilariae and 3.45-17.87 µM for adult males. Homology modeling was used to generate a 3D model of the thioredoxin reductase target and docking simulation, followed by molecular dynamics and binding free energy calculations attempted to offer an explanation of the anti-onchocercal structure-activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilarial drugs. The results of this study validate the traditional use of in the treatment of human onchocerciasis.