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

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 mm. compound 5j bearing 4-methylbenzylidene group was found to be the most active compound with ec50 = 90 mm 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.