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

Abstract

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds, voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8), and conoduramine (9), were isolated from the stem bark of Voacanga africana. The structures of the compounds were determined by comprehensive spectroscopic analyses (1D- and 2D-NMR). Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, 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 the O. ochengi thioredoxin reductase target and docking simulation 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 antifilirial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.

Potent Anti-amoebic Effects of Ibogaine, Voacangine and the Root Bark Alkaloid Fraction of Tabernaemontana arborea

“…In contrast, anti-parasite activity has been scarcely studied. As with the amoebae, voacangine and ibogaine have been shown to be highly effective against microfilariae and male adults of Onchocerca ochengi 37 . Moreover, it has been shown that a Tabernaemontana catharinensis extract, rich in voacangine (53%) exhibited potent antileishmanial activity against L. amazonensis 38 .…”

Editorial to Special Issue—“Structure-Activity Relationships (SAR) of Natural Products”

“…This study by Duncan et al could further explain why the NP only showed experimental activity against the mutant, and not the wild type influenza virus. While Jöhrer et al were able to show that the position C-25 of a series of terpenooids from Black Cohosh ( Actaearacemosa ) could increase their cytotoxic effects, the arabinose moiety at position C-3 having an impact on this activity, Babiaka et al used molecular docking of mono- and bis-indole alkaloids towards a homology model of Onchocerca ochengi thioredoxin reductase to attempt an explanation of the anti-filarial activities of these compounds [ 24 ]. Kumar et al combined several in vitro, in silico, and in vivo experiments to investigate the anti-anaphylactoid activity of Genistein in order to understand the possible molecular mechanisms of its action, which is mediated by a family of GPCRs [ 25 ].…”