Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives.
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.
Santos
Fernanda da C
Fda C
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.
Abreu
Paula
P
Castro
Helena C
HC
Paixão
Izabel C P P
IC
Cirne-Santos
Claudio C
CC
Giongo
Viveca
V
Barbosa
Juliana E
JE
Simonetti
Bruno R
BR
Garrido
Valéria
V
Bou-Habib
Dumith Chequer
DC
Silva
David de O
Dde O
Batalha
Pedro N
PN
Temerozo
Jairo R
JR
Souza
Thiago M
TM
Nogueira
Christiane M
CM
Cunha
Anna C
AC
Rodrigues
Carlos R
CR
Ferreira
Vitor F
VF
de Souza
Maria C B V
MC
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
D019380:Anti-HIV Agents; D015363:Quinolones