ABSTRACT
Despite the success of highly active antiretroviral therapy, AIDS still remains as one of the most important world health problems. Toxicity of current available drugs and inevitable emergence of multi-drug resistant strains makes things worse. In the present study a series of novel Biginelli-type pyrimidine compounds were evaluated as potential anti-human immunodeficiency virus (HIV)-1 agents using green fluorescence protein (GFP) reporter single round HIV-1 infection assay. The rate of infected cells was monitored by flowcytometry. The effect of compounds on the cellular proliferation was considered as the cyotoxicity. The anti-HIV-1 active compounds were selected for HIV-1 replication and syncytium formation assays. The antiretroviral activity of compounds was measured against luciferase reporter A murine leukemia virus (AMLV) virions as the retrovirus control. Compounds 2, 5, 6, 8, 11, 12, 13, 17, 18, 20, and 21 were the most potent against HIV-1. Compound 8 had the 50% inhibitory concentration (IC50) of 100 nmol/l for inhibiting HIV-1 replication and 50% cytotoxic concentration (CC50) was up to 100 µmol/l (therapeutic index (TI) >1000). Results show that the active compounds were able to inhibit the retrovirus control as well. Analysis of structure of the studied compounds proved relationships with their anti-HIV-1 effects. Some of the studied compounds seem to be promising anti-HIV-1 drug candidates. Structural manipulation based on the well-defined structure-activity relationships might propose some new leads for anti-HIV-1 drug discovery programs.
