Design, Synthesis and Evaluation of Pyrido [1,2] a benzimidazoles derivatives as Anti-malarial Efficacy

Abstract

Quantitative structure–activity relationship (QSAR) analysis and molecular docking were conducted on 40 benzimidazole analogues to investigate their antimalarial potential. A dataset comprising 32 training compounds was used to develop comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) models. The developed models demonstrated promising statistical performance, with reported predictive (r^2) values of 0.882, 0.788, and 0.867 for CoMFA, CoMSIA, and HQSAR, respectively. Molecular docking was additionally performed against the Plasmodium falciparum protein structure identified by PDB ID 2ANL to investigate the potential binding interactions of the designed compounds within the target binding site. Guided by the computational findings, 15 styryl benzimidazole derivatives were designed, synthesized, structurally characterized, and evaluated for their antimalarial activity. The experimental activity data were subsequently examined using CoMFA and CoMSIA analyses to assess the relationship between molecular features and biological activity. Collectively, these computational and experimental investigations provide a basis for identifying promising benzimidazole derivatives for further antimalarial drug development.

Keywords: CoMFA; CoMSIA; HQSAR and docking; studies as Plasmodium falciparum