Submit Manuscript  

Article Details


Novel 4-Oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors: Synthesis, Docking Studies, Molecular Dynamics Simulation and Biological Activities

Author(s):

Elnaz Ebrahim Zadeh, Rouhollah Vahabpour, Amirreza Dowlati Beirami, Zahra Hajimahdi and Afshin Zarghi*   Pages 1 - 12 ( 12 )

Abstract:


Background: HIV-1 integrase (IN) has been considered as an important target for the development of novel antiHIV-1 drugs.

Objective: The aim of study is to design a novel groups of HIV IN inhibitors.

Method: In this study, we presented a novel series of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic acid derivatives by structural modification of N-arylindole -diketoacids as a well-known group of IN inhibitors.

Results: Based on in-vitro anti-HIV-1 activity in cell-based assay, compounds 5, 6a and 6k displayed moderate to good inhibitory activity with EC50 values of 4.14, 1.68 and 0.8 M, respectively. However, integrase inhibition assay showed that most of analogues did not have significant effects against integrase enzyme except compound 5 with IC50 value of 45 M. Our results indicated that compound 6k was the best one among synthesized compounds with an EC50 of 0.8 M and SI of 175. Docking and molecular dynamics simulation studies were also performed to provide some insights into probable mechanism of tested compounds.

Conclusion: These findings suggest that 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic acid derivatives may consider as promising lead compounds for development of new anti-HIV-1 drugs.

Keywords:

s: HIV-1 integrase; Benzo[4, 5]imidazo[1, 2-a]pyrimidine-3-carboxylic acid; Synthesis, Molecular dynamics, Dockin

Affiliation:

Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Medical Lab Technology Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran



Read Full-Text article