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Current HIV Research

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ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

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Research Article

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

Author(s): Zahra Hajimahdi, Rezvan Zabihollahi, Mohamad Reza Aghasadeghi and Afshin Zarghi*

Volume 17, Issue 3, 2019

Page: [214 - 222] Pages: 9

DOI: 10.2174/1570162X17666190911125359

Price: $65

Abstract

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.

Keywords: Synthesis, molecular docking, design, anti-HIV-1 activity, integrase, 4-quinazolinone.

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