Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Smith Babiaka
,
Conrad Simoben
ORCID logo ,
Kennedy Abuga
,
James Mbah
,
Rajshekhar Karpoormath
ORCID logo ,
Dennis Ongarora
,
Hannington Mugo
,
Elvis Monya
,
Fidelis Cho-Ngwa
,
Wolfgang Sippl
ORCID logo ,
Joel Loveridge
,
Fidele Ntie-Kang
* ORCID logo
Version 1 : Received: 16 November 2020 / Approved: 17 November 2020 / Online: 17 November 2020 (11:13:54 CET)

A peer-reviewed article of this Preprint also exists.

Babiaka, S.B.; Simoben, C.V.; Abuga, K.O.; Mbah, J.A.; Karpoormath, R.; Ongarora, D.; Mugo, H.; Monya, E.; Cho-Ngwa, F.; Sippl, W.; Loveridge, E.J.; Ntie-Kang, F. Alkaloids with Anti-Onchocercal Activity from Voacanga africana Stapf (Apocynaceae): Identification and Molecular Modeling. Molecules 2021, 26, 70. Babiaka, S.B.; Simoben, C.V.; Abuga, K.O.; Mbah, J.A.; Karpoormath, R.; Ongarora, D.; Mugo, H.; Monya, E.; Cho-Ngwa, F.; Sippl, W.; Loveridge, E.J.; Ntie-Kang, F. Alkaloids with Anti-Onchocercal Activity from Voacanga africana Stapf (Apocynaceae): Identification and Molecular Modeling. Molecules 2021, 26, 70.

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.

Keywords

Alkaloids; Anti-Onchocercal; Bisindoles; Docking; Homology Modeling; Monoindoles.

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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