Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 8-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazides as Potential Anti-HIV Agents

Iran J Pharm Res. 2022 May 17;21(1):e123962. doi: 10.5812/ijpr-123962. eCollection 2022 Dec.


Background: The development of a highly safe and potent scaffold is a significant challenge in anti-HIV drug discovery.

Objectives: This study aimed at developing a novel series of anti-HIV agents based on HIV integrase inhibitor pharmacophores.

Methods: A novel series of 8-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives featuring various substituted benzoyl and N-phenyl carboxamide and carbothioamide moieties were designed and synthesized.

Results: According to the biological evaluation, all the developed compounds were effective against HIV at concentrations lower than 150 µM, associated with no significant cytotoxicity (CC50 > 500 µM).

Conclusions: Compound 8b, possessing a 4-fluorobenzoyl group, was the most potent compound, with an EC50 of 75 µM. Docking studies revealed that the binding modes of designed compounds are similar to the known HIV integrase inhibitors.

Keywords: 4-oxo-1,4-dihydroquinoline-3-carbohydrazide; Anti-HIV; HIV Integrase; Molecular Modeling; Synthesis.