Microwave Assisted One-Pot Synthesis of Fused[1,2,3]Triazolo[4′,5′:3,4]Pyrrolo[1,2-c]Pyrimidines as Potent Anticancer Agents

Abstract

Synthetic chemists have organized easy and effective ways to achieve perfect synthesis in response to the requirement for scaffolds that are crucial for medical applications. A general strategy was developed for the synthesis of fused [1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2-c]pyrimidines using one-pot CuI-catalyzed cycloaddition followed by C─C bong coupling. The cancer activity of the synthesized compounds was then tested in vitro against two lung cancer cell lines and some compounds showed potent activity compared to the primary standard, 5-FU. We also found EGFR properties in the potent compounds and the results showed that compounds 1-(3,5-difluorophenyl)-7-methyl-1,4-dihydro-6H-[1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2-c]pyrimidine-6,8(7H)-dione, and 1-(3,5-dichlorophenyl)-7-methyl-1,4-dihydro-6H-[1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2-c]pyrimidine-6,8(7H)-dione were strong EGFR inhibitors compared to remaining compounds. We also carried out in silico studies to assess the molecular interactions of more potent compounds with EGFR proteins (PDB: 4HJO). Our findings revealed that all potent compounds exhibited more binding interactions than standard erlotinib (-7.69 K cal/mol) with binding energies from −8.22 to −9.45 K cal/mol.