Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling
Smith B. Babiaka,
Conrad V. Simoben,
Kennedy O. Abuga,
James A. Mbah,
Rajshekhar Karpoormath,
Dennis Ongarora,
Hannington Mugo,
Elvis Monya,
Fidelis Cho-Ngwa,
Wolfgang Sippl,
Edric Joel Loveridge,
Fidele Ntie-Kang
Affiliations
Smith B. Babiaka
Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon
Conrad V. Simoben
Institute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle, Germany
Kennedy O. Abuga
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Nairobi, Nairobi P.O. Box 19676–00202, Kenya
James A. Mbah
Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon
Rajshekhar Karpoormath
Department of Pharmaceutical Chemistry, School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa
Dennis Ongarora
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Nairobi, Nairobi P.O. Box 19676–00202, Kenya
Hannington Mugo
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Nairobi, Nairobi P.O. Box 19676–00202, Kenya
Elvis Monya
ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon
Fidelis Cho-Ngwa
ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon
Wolfgang Sippl
Institute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle, Germany
Edric Joel Loveridge
Department of Chemistry, Swansea University, Singleton Park, Swansea SA2 8PP, UK
Fidele Ntie-Kang
Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon
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 Voacangaafricana. The structures of the compounds were determined by comprehensive spectroscopic analyses. 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 O. ochengi 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 V. africana in the treatment of human onchocerciasis.
