Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives

• Published in: Bioorganic & medicinal chemistry 2009-08, Vol.17 (15), p.5476-5481
• Main Authors: Santos, Fernanda da C., Abreu, Paula, Castro, Helena C., Paixão, Izabel C.P.P., Cirne-Santos, Claudio C., Giongo, Viveca, Barbosa, Juliana E., Simonetti, Bruno R., Garrido, Valéria, Bou-Habib, Dumith Chequer, Silva, David de O., Batalha, Pedro N., Temerozo, Jairo R., Souza, Thiago M., Nogueira, Christiane M., Cunha, Anna C., Rodrigues, Carlos R., Ferreira, Vitor F., de Souza, Maria C.B.V.
• Format: Article
• Language: English
• Subjects: Animals; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral; Antiviral activity; Antiviral agents; Biological and medical sciences; Cell Survival - drug effects; Cercopithecus aethiops; HIV Infections - drug therapy; HIV-1; HIV-1 - drug effects; HIV-1 - growth & development; Human immunodeficiency virus 1; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - virology; Medical sciences; Models, Molecular; Molecular Structure; Oxoquinoline; Pharmacology. Drug treatments; Quinolones - chemical synthesis; Quinolones - chemistry; Quinolones - pharmacokinetics; Quinolones - pharmacology; Structure-Activity Relationship; Structure–activity relationship (SAR); Vero Cells
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.06.037

In the present article, we describe the synthesis, anti-HIV1 profile and molecular modeling evaluation of 11 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.