Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives
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- 作者：Fern ; a da C. Santos ; Paula Abreu ; Helena C. Castro ; Izabel C.P.P. Paixã ; o ; Claudio C. Cirne-Santos ; Viveca Giongo ; Juliana E. Barbosa ; Bruno R. Simonetti ; Valé ; ria Garrido ; Dumith Chequer Bou-
- 关键词：Antiviral ; HIV-1 ; Oxoquinoline ; Structure– ; activity relationship (SAR)
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2009
- 出版时间：1 August 2009
- 年：2009
- 卷：17
- 期：15
- 页码：5476-5481
- 全文大小：431 K
文摘
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.