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.
Investigation about the Inhibition of HIV-1 Gp41 Fusion via Andrographis Paniculata: Virtual Screening, Molecular Dynamics Simulation and Free Energy Calculation