Potential of Curry Leaf Compounds as PfAP4AH Inhibitors: In Silico Study.

Abstract

Diadenosine tetraphosphate hydrolase of Plasmodium falciparum (PfAp4AH) catalyzes the hydrolysis of diadenosine tetraphosphate into adenosine monophosphate (AMP). Curry leaf (Murraya koenigii) is a plant species rich in carbazole alkaloids and possesses antimalarial properties. This study aims to identify potential inhibitors for the PfAp4AH enzyme from the screening of 156 active compounds derived from curry leaves, in silico. The molecular docking tools used were Google Colab, AutoDock 4, and AutoDock Vina to assess the Gibbs free energy (?G) and ligand interactions with the target amino acid residues (Tyr87, Pro133, and Ser135) that can interact with the ATP adenine ring. The analysis results identified ten active compounds with the best ?G values and stability in binding to PfAp4AH. The compound 1-(2-hydroxy-3-methyl-9H-carbazole-1-yl)-3-methyl-9H-carbazole-2-ol is the most promising ligand, with a ?G value of -8.0 kcal/mol. Bikoeniquinone A and 3,3'-[Oxybis(methylene)]bis(9- methoxy-9H-carbazole) demonstrated effective interaction with key target residues, thereby underscoring the potential of compounds derived from the curry leaf tree as promising inhibitors of PfAp4AH. These findings provide a significant foundation for further investigation and development of these compounds as potential antimalarial agents