Synthesis of pyrazolo[5',1':2,3]imidazo[1,5- c]quinazolin-6(5 H)-ones and molecular docking study of their affinity against the COVID-19 main protease

Shaghayegh Saeedi; Abbas Rahmati; Zahra Chavoshpour-Natanzi

doi:10.1039/d2ra03179e

Synthesis of pyrazolo[5',1':2,3]imidazo[1,5- c]quinazolin-6(5 H)-ones and molecular docking study of their affinity against the COVID-19 main protease

RSC Adv. 2022 Jul 8;12(30):19579-19589. doi: 10.1039/d2ra03179e. eCollection 2022 Jun 29.

Authors

Shaghayegh Saeedi¹, Abbas Rahmati¹, Zahra Chavoshpour-Natanzi¹

Affiliation

¹ Department of Chemistry, University of Isfahan P. O. Box 81746-73441 Isfahan Iran a.rahmati@sci.ui.ac.ir +98 31 37934943.

Abstract

A novel series of fused pyrazolo[5',1':2,3]imidazo[1,5-c]quinazolin-6(5H)-ones were synthesized and their affinity against the COVID-19 main protease was investigated using molecular docking study and compared to that of some used standard clinical drugs. These compounds were obtained in good to excellent yields from 63 to 91% in the presence of 30 mol% catalyst in ethanol at reflux for 2 h through an efficient one-pot three-component reaction including an intramolecular rearrangement and a cyclization through intramolecular nucleophilic reaction. The results of in silico studies showed that electronegativity, resonance effects, hydrophobic interaction, halogen and hydrogen bonding had significant effects on the performance of these compounds as an inhibitor ligand. Also, these results indicated the proper affinity of these compounds against the COVID-19 main protease with excellent binding energies (especially 4r = -8.77, 4q = -8.73 and 4m = -8.63) in comparison to remdesivir, chloroquine, hydroxychloroquine, molnupiravir and nirmatrelvir drugs.