Title of article :
Design, Synthesis, Molecular Modeling Study and Biological Evaluation of New N'-arylidene-pyrido[2,3-d]pyrimidine-5-carbohydrazide Derivatives as Anti-HIV-1 Agents
Author/Authors :
Ebrahimzadeh, Elnaz Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Hajimahdi, Zahra Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Zarghi, Afshin Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Vahabpour Rodsar, Roholah Medical Lab Technology Department - School of Allied Medical Sciences - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Tabatabai, Sayyed Abbas Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract :
In an attempt to identify potential new agents that are active against HIV-1, a series of novel pyridopyrimidine-5-carbohydrazide derivatives featuring a substituted benzylidene fragment were designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors. The cytotoxicity profiles of these compounds showed no significant toxicity to human cells and they exhibited anti-HIV-1 activity with EC50 values ranging from 90 to 155 M. Compound 5j bearing 4-methylbenzylidene group was found to be the most active compound with EC50 = 90 M and selectivity index, CC50/EC50 = 6.4. Molecular modeling studies indicated the capacity of compound 5j to interact with two Mg2+ cations and several residues that are important in HIV-1 integrase inhibition. These findings suggested that pyridopyrimidine-5-carbohydrazide scaffold might become a promising template for development of novel anti-HIV-1 agents.
Keywords :
Synthesis , Pyridopyrimidine-5-carbohydrazide , Anti-HIV-1 , Molecular modeling , HIV-1 integrase
