新型8-甲基-4-氧代-1,4-二氢喹啉-3-碳酰肼作为潜在抗HIV药物的合成、生物学评价及分子模拟研究
Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 8-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazides as Potential Anti-HIV Agents.
作者信息
Alemi Mehrdad, Kamali Fatemeh, Vahabpour Roudsari Rouhollah, Hajimahdi Zahra, Zarghi Afshin
机构信息
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Medical Lab Technology Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
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 (CC > 500 µM).
CONCLUSIONS
Compound 8b, possessing a 4-fluorobenzoyl group, was the most potent compound, with an EC of 75 µM. Docking studies revealed that the binding modes of designed compounds are similar to the known HIV integrase inhibitors.
背景
开发一种高度安全且有效的支架是抗HIV药物发现中的一项重大挑战。
目的
本研究旨在基于HIV整合酶抑制剂药效团开发一系列新型抗HIV药物。
方法
设计并合成了一系列新型的8-甲基-4-氧代-1,4-二氢喹啉-3-碳酰肼衍生物，其具有各种取代的苯甲酰基以及N-苯基甲酰胺和碳硫酰胺部分。
结果
根据生物学评估，所有开发的化合物在浓度低于150μM时对HIV有效，且无明显细胞毒性（CC>500μM）。
结论
具有4-氟苯甲酰基的化合物8b是最有效的化合物，其EC为75μM。对接研究表明，设计化合物的结合模式与已知的HIV整合酶抑制剂相似。
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