Background: The emergence of drug-resistant viral strains has created the need for the
development of novel anti-HIV agents with a diverse structure that targets key enzymes in the HIV
Objective: Considering the pharmacophore of integrase inhibitors, one of the validated targets for
anti-HIV therapy, we designed a quinazolinone incorporated coumarin scaffold to affect HIV.
Methods: Coumarin is a beta enol ester and also a well-known drug scaffold. Designed structures
were prepared using a one-pot three-component reaction from 3-amino-4-hydroxycoumarin, isatoic
anhydride and benzaldehyde derivatives.
Results: In vitro anti-HIV and cytotoxicity assay indicated that more than half of the compounds
had EC50 values lower than 50 µM. Unsubstituted phenyl derivative showed the highest activity and
selectivity with an EC50 value of 5 µM and a therapeutic index of 7. Compounds were docked into
the integrase active site to investigate the probable mechanism of action. Accordingly, the hydroxyl
moiety of coumarin along with the carbonyl of the quinazolinone ring could function as the metal
chelating group. Quinazolinone and phenyl groups interact with side chains of IN residues, as well.
Conclusion: Here, a novel anti-HIV scaffold is represented for further modification and in-vivo