title: Design, synthesis and docking studies of new 4-hydroxyquinoline-3-carbohydrazide derivatives as anti-HIV-1 agents.
abstract: A new class of 4-hydroxyquinoline-3-carbohydrazide derivatives was prepared and evaluated for its anti-HIV activity. The primary bioassay results indicated that most of tested compounds possess moderate inhibitory properties against HIV-1 virus (NL4-3) in Hela cells cultures. Our results also indicated that compounds 6d and 7e were the most potent anti-HIV agents among the synthesized compounds with inhibition rate of 32 and 28% at concentration of 100 μM, respectively. A docking study using the later crystallographic data available for PFV integrase including its complexes with Mg2+ and raltegravir, showed that the designed compounds bind into the active site of integrase such that carboxylic and hydroxyl groups of 4-hydroxyquinoline-3-carbohydrazide chelate the Mg2 + ion. Interestingly, all of the synthesized compounds were found to present no significant cytotoxicity at concentration of 100 μM. Therefore, these compounds can provide a very good basis for the development of new anti-HIV-1 agents.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Z
authors.initials: Z
authors.lastname: Hajimahdi
authors.forename: R
authors.initials: R
authors.lastname: Zabihollahi
authors.forename: M R
authors.initials: MR
authors.lastname: Aghasadeghi
authors.forename: A
authors.initials: A
authors.lastname: Zarghi
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003461:Crystallography; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular
chemical_list: D019380:Anti-HIV Agents; D006834:Hydrazines; D006912:Hydroxyquinolines; C019289:carbohydrazide