Synthesis and biological evaluation of HQCAs with aryl or benzyl substituents on N-1 position as potential HIV-1 integrase inhibitors.
ABSTRACT A series of new 5-hydroxylquinolone-3-carboxylic acids (HQCAs) with various aryl or benzyl substituents on N-1 position were synthesized and evaluated for their anti-HIV activity in C8166 cell culture. Most of the target compounds displayed activity against wide-type HIV-1 in the low micromolar range in infected C8166 cells. The most active compound 5 g exhibited activity against wild-type HIV-1 and HIV-1 mutant virus A17 with an EC(50) value of 3.17 and 17.88 μM, respectively. The biological results and the docking study revealed that the substitution pattern on N-1 position of the quinolone core might contribute to physicochemical properties of HQCAs and resulted in great influence on their antiviral potency.
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ABSTRACT: A series of new quinolone-3-carboxylic acids as HIV-1 integrase inhibitors featuring a fluorine atom at C-5 position were synthesized and evaluated for their antiviral activity in C8166 cell culture. These newly synthesized compounds showed anti-HIV activity against wild-type virus with an EC(50) value ranging from 29.85 to 0.032 μΜ. The most active compound 4e exhibited activity against wild-type virus and the mutant virus A17 with an EC(50) value of 0.032 and 0.082 μΜ, respectively. Preliminary structure-activity relationship of these 5-fluoroquinolone-3-carboxylic acids was also investigated.Journal of Enzyme Inhibition and Medicinal Chemistry 04/2012; · 1.50 Impact Factor