Synthesis,antiviral activity and molecular modeling of oxoquinoline derivatives |
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Authors: | Fernanda da C Santos Paula Abreu Helena C Castro Izabel CPP 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 CBV de Souza |
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Institution: | 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;2. Universidade Federal Fluminense, Instituto de Biologia, Departamento de Biologia Celular e Molecular, Programa de Pós Graduação em Neurociências, Outeiro de São João Batista s/n, Centro, Niterói, CEP 24020-150, RJ, Brazil;3. Laboratório de Modelagem Molecular e QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, CEP 21941-590, RJ, Brazil;4. Laboratório de Pesquisas Sobre o Timo, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, RJ 21045-900, Brazil |
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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 R2 and R3 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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