Iboga-Indole Alkaloids as Potential Plasmodial Inhibitors: Identification, Biosynthesis, and Molecular Docking...

Area of Science:

• Natural Products Chemistry
• Medicinal Chemistry
• Parasitology

Background:

• Voacanga africana is a source of bioactive indole alkaloids.
• Malaria remains a significant global health challenge, necessitating the discovery of new antimalarial agents.

Purpose of the Study:

• To isolate and characterize alkaloids from Voacanga africana stem bark.
• To evaluate the in vitro antiplasmodial activity of isolated alkaloids.
• To explore the structure-activity relationship of these alkaloids against Plasmodium falciparum.

Main Methods:

• Isolation and structural elucidation of alkaloids using NMR spectroscopy.
• In vitro antiplasmodial activity assay against a chloroquine-sensitive Plasmodium falciparum strain.
• Computational methods including protein-ligand co-folding and molecular dynamics simulations.

Main Results:

• Four alkaloids were isolated: voacamine A (new), voacamine, voacorine, and voacangine.
• Voacamine (2) and voacorine (3) exhibited potent antiplasmodial activity with IC50 values of 5.734 ± 1.365 and 5.319 ± 2.206 µg/mL, respectively.
• Molecular modeling studies provided insights into the antimalarial structure-activity relationship.

Conclusions:

• Voacamine and voacorine are promising lead compounds for antimalarial drug development.
• Further investigation into these alkaloids could lead to novel therapeutic strategies against malaria.