Design, Synthesis and Docking studies of New Quinazolinone Derivatives as Anti-HIV-1 Agents: Quinazolinone Derivatives as Anti-HIV-1 Agents
نویسندگان
1 Medical Lab Technology Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2 Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3 Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4 Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
5 Active Pharmaceutical Ingredients Research Center (APIRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
6 Active Pharmaceutical Ingredients Research Center (APIRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
7 Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
doi
10.22037/ijps.v18.41376چکیده
The Human Immunodeficiency Virus (HIV) infection is a global health challenge that creates an urgent need to develop new therapeutic agents. In this work, a new group of quinazolinone derivatives were designed and synthesized and evaluated their anti-HIV activity. The antiviral assay revealed that some analogues inhibited HIV replication in the cell culture. A docking study using the later crystallographic data available for PFV integrase including its complexes with Mg2+ and dolutegravir, showed that the designed compounds bind into the active site of integrase enzyme such that both carbonyl groups chelate Mg2+ ions. Interestingly, all of the synthesized compounds were found to present no significant cytotoxicity at a concentration of 100 μM. According to the anti-HIV evaluation results, the compound 10f was found as the most active with the inhibition rate of 38%. Therefore, these compounds can provide a very good basis for the development of new anti-HIV agents.
