One-pot synthesis, anticancer, EGFR and caspases assays of novel fused [1,2,3]triazolo-pyrrolo[2,1-b]quinazolinones

In this study, we designed and synthesized several novel fused [1,2,3]triazolo [4 ',5 ':3,4]pyrrolo[2,1-b]quinazolinone derivatives using a single [3 + 2] reaction cycloaddition reaction of 6,7-dichloro-3-(3-iodoprop-2-yn-1-yl) quinazolin-4(3H)-one (3) followed by C-C bond coupling with various aryl azides in a PEG-400 medium. All of the newly synthesized compounds were evaluated in vitro anti-breast cancer activity against MDA-MB-231 and MCF-7 cell lines. When compared to the reference molecule, erlotinib, the majority of the compounds demonstrated adequate efficacy. The most promising compounds, 4k, 4j, and 4g, demonstrated excellent anticancer activity against the MCF-7 cell line, with IC50 values ranging from 1.91 +/- 0.34 and 3.55 +/- 0.86, and 3.68 +/- 0.39 mu M, respectively, as well as excellent kinase inhibitory activities (EGFR: IC50 = 0.35 +/- 0.24, 0.50 +/- 0.15, and 0.42 +/- 0.08 mu M). The more potent compounds significantly initiated the activation of 3/7, 8, and 9 caspases at 05, 10, and 15 mu g/ml and slightly dropped at 20 mu g/ml of the compound concentration. In silico investigations of three powerful compounds (4 g, 4j, and 4k) were also performed to detect their interactions with the EGFR receptor, and the energy estimates were consistent with the reported IC50 values.