Molecular Modeling Studies and Synthesis of Isocryptolepine Derivatives as Antimalarial Using Docking, CoMFA, CoMSIA, and HQSAR.

Abstract

Background: Our research highlights the synthesis of newer antimalarial compounds using molecular modeling studies.

Objective: The study investigates a series of isocryptolepine derivatives from previous literature, focusing on their biological activities as antimalarial agents.

Methods: Computational methods such as molecular docking and QSAR were employed to gain insights into the interaction between the synthesized compounds and the target enzyme PfDHFR-TS.

Results: Molecular docking studies helped to identify key binding interactions, supporting the design of more effective compounds. Using CoMFA and CoMSIA, the study explored steric, electrostatic, and hydrogen-bonding fields, providing a quantitative structure-activity relationship (QSAR) for 49 compounds.

Conclusion: The CoMFA model yielded strong predictive r² values of 0.971, while the CoMSIA model highlighted the significance of hydrophobic and hydrogen bond interactions. These findings inform the design of novel isocryptolepine derivatives with improved antimalarial activity.