Synthesis and biological evaluation of HQCAs with aryl or benzyl substituents on N-1 position as potential HIV-1 integrase inhibitors.

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.