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A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (<b>1</b>), along with eight known compounds—voacangine (<b>2</b>), voacristine (<b>3</b>), coronaridine (<b>4</b>), tabernanthine (<b>5</b>), iboxygaine (<b>6</b>), voacamine (<b>7</b>), voacorine (<b>8</b>) and conoduramine (<b>9</b>)—were isolated from the stem bark of <i>Voacangaafricana</i>. The structures of the compounds were determined by comprehensive spectroscopic analyses. Compounds <b>1</b>, <b>2</b>, <b>3</b>, <b>4</b>, <b>6</b>, <b>7</b> and <b>8</b> were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of <i>Onchocerca ochengi</i>, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC₅₀ 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 <i>O. ochengi</i> 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 <i>V. africana</i> in the treatment of human onchocerciasis.