Design, Synthesis and Docking Studies of Thioimidazolyl Diketoacid Derivatives Targeting HIV-1 Integrase.

BACKGROUND Integrase enzyme is a validated drug target to discover novel structures as anti-HIV-1 agents. OBJECTIVE Novel series of thioimidazolyl diketo acid derivatives characterizing various substituents at N-1 and 2-thio positions of central ring were developed as HIV-1 integrase inhibitors. RESULTS The obtained molecules were evaluated in the enzyme assay, displaying promising integrase inhibitory activity with IC50 values ranging from 0.9 to 7.7 M. The synthesized compounds were also tested for antiviral activity and cytotoxicity using HeLa cells infected by the single-cycle replicable HIV-1 NL4-3. CONCLUSION The most potent compound was 18i with EC50=19 µM, IC50 0.9 µM and SI= 10.5. Docking studies indicated that the binding mode of the active molecule is well aligned with the known HIV-1 integrase inhibitors.