title: Some hydrazones of 2-aroylamino-3-methylbutanohydrazide: synthesis, molecular modeling studies, and identification as stereoselective inhibitors of HIV-1.
abstract: In accordance with our antiviral drug development attempt, acylhydrazone derivatives bearing amino acid side chains were synthesized for the evaluation of their antiviral activity against various types of viruses. Among these compounds, 8(S) , 11(S) , and 12(S) showed anti-HIV-1 activity with a 50% inhibitory concentration (IC(50)) =123.8 µM (selectivity index, SI>3), IC(50) =12.1 µM (SI>29), IC(50) =17.4 µM (SI>19), respectively. Enantiomers 8(R) , 11(R) , and 12(R) were inactive against the HIV-1 strain III(B) . Hydrazones 8(S) , 11(S) , and 12(S) which were active against HIV-1 wild type showed no inhibition against a double mutant NNRTI-resistant strain (K103N;Y181C). Molecular docking calculations of R- and S-enantiomers of 8, 11, and 12 were performed using the hydrazone-bound novel site of HIV-1 RT.
authors.affiliation: Department of Pharmaceutical Chemistry, Marmara University, Haydarpaşa, İstanbul, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Tatar
authors.forename: Ilkay
authors.initials: I
authors.lastname: Küçükgüzel
authors.forename: Dirk
authors.initials: D
authors.lastname: Daelemans
authors.forename: Tanaji T
authors.initials: TT
authors.lastname: Talele
authors.forename: Neerja
authors.initials: N
authors.lastname: Kaushik-Basu
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018929:Cell Culture Techniques; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D019380:Anti-HIV Agents; D006835:Hydrazones