2. Academic Validation
  3. Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives

Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives

  • Bioorg Med Chem. 2009 Aug 1;17(15):5476-81. doi: 10.1016/j.bmc.2009.06.037.
Fernanda da C Santos 1,  Paula Abreu,  Helena C Castro,  Izabel C P P Paixão,  Claudio C Cirne-Santos,  Viveca Giongo,  Juliana E Barbosa,  Bruno R Simonetti,  Valéria Garrido,  Dumith Chequer Bou-Habib,  David de O Silva,  Pedro N Batalha,  Jairo R Temerozo,  Thiago M Souza,  Christiane M Nogueira,  Anna C Cunha,  Carlos R Rodrigues,  Vitor F Ferreira,  Maria C B V de Souza
Affiliations

Affiliation

  • 1 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.
PMID: 19581097 DOI: 10.1016/j.bmc.2009.06.037
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.

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