Rational Design and In Silico Evaluation of Benzimidazole Derivatives as Potential Antimalarial Agents

Abstract

Quantitative Structure–Activity Relationship (QSAR) and molecular docking studies were performed on a series of 40 benzimidazole analogues to identify structural features associated with antimalarial activity. CoMFA, CoMSIA, and HQSAR models developed using a training set of 32 compounds demonstrated good statistical reliability and predictive ability. Molecular docking against the Plasmodium falciparum* target protein (PDB ID: 2ANL) revealed favorable binding interactions, supporting the design of more potent antimalarial candidates. Based on the computational results, 15 novel benzimidazole derivatives were designed, synthesized, characterized, and evaluated for their antimalarial activity. The experimental results further validated the developed QSAR models, confirming their usefulness in the rational design of new antimalarial agents. Keywords: Benzimidazole; Antimalarial drug discovery; QSAR modeling; CoMFA; CoMSIA; Molecular docking; Plasmodium falciparum; Structure-based drug design