In silico Antiplasmodial and Anti-inflammatory Activities of Compounds derived from Anogeissus leiocarpus

Abstract

Background: Over expression of inflammatory cytokines causes severity of malaria, and due to report of drug resistant strains of Plasmodium species, new and effective antimalarial drugs with anti-inflammatory properties are desirable.

Materials and Methods: The compounds present in acetone leaf and stem bark extracts of Anogeissus leiocarpus were identified by Gas Chromatography-Mass Spectrometry (GC-MS) analysis and assessed for their potentials as antimalarial and anti-inflammatory agents, using in silico methods. The compounds identified were docked against Plasmodium falciparum dihydrofolate reductase (PfDHFR), enoyl acyl carrier protein reductase (PfENR) and hexose transporter 1 (PfHT1), using SwissDock online server and the binding interactions were assessed with Ligplot+ tool. Using the same approach, these compounds were also docked against human inflammatory cytokines; interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12). The ADMET (absorption, distribution, metabolism, excretion, toxicity) profiles and drug-like properties of the promising compounds were investigated using admetSAR. Ten and twenty-one compounds were mined from stem bark and leaf, respectively.

Results: From the molecular docking studies, the lead compounds identified to possess both antiplasmodial and anti-inflammatory effects are oleic acid; cyclopropaneoctanal, 2-octyl-; octadec-9-enoic acid; n-Hexadecanoic acid; tetradecanoic acid; N-Glycylglycine; phytol, acetate; phytol and 9,12-Octadecadienoic acid (Z,Z)- with binding energies ranging from -9.60 to -7.27 Kcal/mol. These compounds bind by hydrogen bonds and hydrophobic interactions to key amino acid residues of the targets. The compounds also showed acceptable ADMET profiles and are predicted to be drug-like.

Conclusion: In- silico analysis of Anogeissus leiocarpus confirms the presence of bioactive anti-plasmodial and anti-inflammatory agents with safe ADMET profile. However, further investigation may be needful for confirmation of these beneficial effects.