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

Mehrdad Alemi; Fatemeh Kamali; Rouhollah Vahabpour Roudsari; Zahra Hajimahdi; Afshin Zarghi

doi:10.5812/ijpr-123962

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.

Authors

Mehrdad Alemi¹, Fatemeh Kamali¹, Rouhollah Vahabpour Roudsari², Zahra Hajimahdi¹, Afshin Zarghi¹

Affiliations

¹ Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Medical Lab Technology Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

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.