Synthesis and Biological Evaluation of N-(4-Fluorophenyl)-6-Methyl-2-Oxo-1, 2, 3, 4-Tetrahydropyrimidine-5-Carboxamides as HIV Integrase Strand Transfer Inhibitors

摘要

HIV-1 integrase (IN) catalyzes chromosomal integration of synthesized viral DNA into host DNA by performing two independent reactions, 3′-processing (3′-P) and strand transfer (ST). In the present study, we report synthesis and evaluation of N-(4-fluorophenyl)-6-methyl-2-oxo-4-substituted phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamides for IN inhibitory activity. All the derivatives were found to inhibit strand transfer reaction in vitro in isolated enzyme assay and most active compound (13e) showed IC50 value of 0.65 μM. Docking studies were also done to justify the IN inhibition and in vitro-in silico correlation was drawn. However, these compounds did not show HIV-1 and HIV-2 inhibition below their cytotoxic concentration in cell culture assay indicating that these compounds cannot be used as lead for anti-HIV activity.