[en] A previously undescribed iboga-indole alkaloid, voacamine A (1), and the known alkaloids, voacamine (2), voacorine (3), and voacangine (4) were isolated from the stem bark of Voacanga africana. The structures of the alkaloids were established by one- and two-dimensional nuclear magnetic resonance analyses as well as by comparison with published data. The antiplasmodial activity of the alkaloids was assessed on a chloroquine-sensitive 3D7 Plasmodium falciparum (Pf3D7) strain, and the half-maximal inhibitory concentration (IC50) values were determined. Alkaloids 2 and 3 showed good in vitro antiplasmodial activity with IC50 values of 5.734 ± 1.365 and 5.319 ± 2.206 µg/mL, respectively, at the concentration tested. A plausible biogenetic pathway of the bisindole alkaloids has been proposed. Protein-ligand co-folding was used to generate protein-ligand complexes for the pfATP6 protein target and the isolated alkaloids. The stability of the modelled complexes was evaluated using molecular dynamics simulation. Scoring metrics of the generated complexes coupled to molecular mechanics generalized-born solvation rescoring of the modelled ligand poses were employed to explain the antimalarial structure-activity relationship for the investigated compounds. Alkaloids 2 and 3 can be considered as possible scaffolds for designing new antiplasmodial lead compounds.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Babiaka, Smith B ; Department of Chemistry, Faculty of Science, University of Buea, Buea, Cameroon ; Department of Microbial Bioactive Compounds, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
Lahngong, Methodius Shinyuy ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Simoben, Conrad V ; Structural Genomics Consortium, University of Toronto, Toronto, Canada
Ongarora, Dennis S B ; Department of Pharmaceutical Chemistry, Pharmaceutics and Pharmacognosy, Faculty of Health Sciences, University of Nairobi, Nairobi, Kenya
Chi, Godloves F ; Department of Chemistry, Faculty of Science, University of Buea, Buea, Cameroon
Tshitenge, Dieudonné T; Small Molecules, R&D Crop Science, Monheim am Rhein, Germany
Karpoormath, Rajshekhar ; Department of Pharmaceutical Chemistry, University of KwaZulu-Natal, Durban, South Africa
Rylands, Marwaan ; Department of Chemistry, University of Cape Town, Cape Town, South Africa
Mbah, James A; Department of Chemistry, Faculty of Science, University of Buea, Buea, Cameroon
Abuga, Kennedy O ; Department of Pharmaceutical Chemistry, Pharmaceutics and Pharmacognosy, Faculty of Health Sciences, University of Nairobi, Nairobi, Kenya
Loveridge, E Joel ; Department of Chemistry, Swansea University, Swansea, UK
Frederich, Michel ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Language :
English
Title :
Iboga-Indole Alkaloids as Potential Plasmodial Inhibitors: Identification, Biosynthesis, and Molecular Docking Studies.
The research was funded by the Alexander von Humboldt Foundation for Georg Forster and Georg Forster\u2010Bayer Research fellowships (Ref. 3.4\u2013CMR\u20131220727\u2013GF\u2010P) at the University of T\u00FCbingen, Germany.The research was funded by the Alexander von Humboldt Foundation for Georg Forster and Georg Forster-Bayer Research fellowships (Ref. 3.4\u2013CMR\u20131220727\u2013GF-P) at the University of T\u00FCbingen, Germany.The research was funded by the Alexander von Humboldt Foundation for Georg Forster and Georg Forster-Bayer Research fellowships (Ref. 3.4\u2013CMR\u20131220727\u2013GF-P) at the University of T\u00FCbingen, Germany.: The research was funded by the Alexander von Humboldt Foundation for Georg Forster and Georg Forster\u2010Bayer Research fellowships (Ref. 3.4\u2013CMR\u20131220727\u2013GF\u2010P) at the University of T\u00FCbingen, Germany. Funding
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