Zahra Hajimahdi, Rezvan Zabihollahi, Mohamad Reza Aghasadeghi and Afshin Zarghi* Pages 214 - 222 ( 9 )
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.
Synthesis, molecular docking, design, anti-HIV-1 activity, integrase, 4-quinazolinone.
Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran