title: Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives.
abstract: In the present article, we describe the synthesis, anti-HIV1 profile and molecular modeling evaluation of 11 oxoquinoline derivatives. The structure-activity relationship analysis revealed some stereoelectronic properties such as LUMO energy, dipole moment, number of rotatable bonds, and of hydrogen bond donors and acceptors correlated with the potency of compounds. We also describe the importance of substituents R(2) and R(3) for their biological activity. Compound 2j was identified as a lead compound for future investigation due to its: (i) high activity against HIV-1, (ii) low cytotoxicity in PBMC, (iii) low toxic risks based on in silico evaluation, (iv) a good theoretical oral bioavailability according to Lipinski 'rule of five', (v) higher druglikeness and drug-score values than current antivirals AZT and efavirenz.
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Programa de Pós-Graduação em Química, Outeiro de São João Batista, s/n, Centro, Niterói, CEP 24210-150, RJ, Brazil.
authors: Fernanda da C
authors: Fda C
authors: Santos
authors: Paula
authors: P
authors: Abreu
authors: Helena C
authors: HC
authors: Castro
authors: Izabel C P P
authors: IC
authors: Paixão
authors: Claudio C
authors: CC
authors: Cirne-Santos
authors: Viveca
authors: V
authors: Giongo
authors: Juliana E
authors: JE
authors: Barbosa
authors: Bruno R
authors: BR
authors: Simonetti
authors: Valéria
authors: V
authors: Garrido
authors: Dumith Chequer
authors: DC
authors: Bou-Habib
authors: David de O
authors: Dde O
authors: Silva
authors: Pedro N
authors: PN
authors: Batalha
authors: Jairo R
authors: JR
authors: Temerozo
authors: Thiago M
authors: TM
authors: Souza
authors: Christiane M
authors: CM
authors: Nogueira
authors: Anna C
authors: AC
authors: Cunha
authors: Carlos R
authors: CR
authors: Rodrigues
authors: Vitor F
authors: VF
authors: Ferreira
authors: Maria C B V
authors: MC
authors: de Souza
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000821:virology; D008958:Models, Molecular; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D019380:Anti-HIV Agents; D015363:Quinolones