Design, Synthesis, Docking Studies and Biological Activities Novel 2,3-Diaryl-4-Quinazolinone Derivatives as Anti-HIV-1 Agents

Background: Although major efforts have been devoted to the effective treatment of HIV-1 infection, it has remained one of the leading causes of deaths around the world. So, development of anti-HIV-1 agents featuring novel structure is essential. Objective: To synthesize novel quinazolinone derivatives and evaluate their anti-HIV-1 activity. Method: In this study, we designed and synthesized a series of novel 2,3-diaryl-4-quinazolinone derivatives using a one-pot multicomponent reaction. Then, the resulting derivatives were evaluated for anti-HIV-1 activity using Hela cell-based single-cycle replication assay. Results: Most of the compounds showed efficacy against HIV-1 replication and the compound 9c exhibited the highest activity with EC50 value of 37 μM. Docking studies indicated that synthesized compounds can interact with the key residues of the HIV-1 integrase active site. Binding of the most active compound was consistent with the HIV-1 integrase inhibitors. Conclusion: Based on our results, these derivatives represent novel lead compounds for the development of new promising anti-HIV-1 agents.