Synthesis, antiproliferative and enzymatic inhibition activities of quinazolines incorporating benzenesulfonamide: Cell cycle analysis and molecular modeling study

The antiproliferative activity of the synthesized quinazolines 2 -22 was evaluated using NCI 60-human tu-mor cell lines. Quinazoline derivatives 5 -8, 11, 14, 15 , and 17 -22 possessed potential antiproliferative ac-tivities against the tested cell lines with positive cytotoxic effects (PCE); 42/59-59/59, and median growth inhibition percentage (MGI%); 22-82%. Among the tested compounds, derivatives 14, 20 , and 21 were the most active antiproliferative agents (MG_MID GI50; 2.13, 3.54, 2.29 mu M, respectively), compared to erlotinib and gefitinib (MG_MID GI50; 7.68 and 2.10 mu M, respectively). Quinazolines 5, 14, 18 , and 20 ex-hibited strong EGFR inhibition activity (IC50; 74.41-100.17 nM), compared to gefitinib and erlotinib (IC50; 53.12 and 105.6 nM, respectively). Whereas derivatives 9, 14 , and 20 possessed potent HER2 inhibition activity (IC50; 51.35-62.87 nM), compared to erlotinib (IC50; 85.93 nM). Derivatives 7, 9 , and 14 revealed the highest inhibitory activity against COX-2 (IC50; 1.75-4.12 mu M) compared to celecoxib (IC50; 2.79 mu M). Molecular docking studies of compound 14 with EGFR, HER2, and COX-2 were performed to generate the binding mode of interactions within the putative pockets.(c) 2023 Elsevier B.V. All rights reserved.

Automated summary

The antiproliferative activity of synthesized quinazolines 2-22 were evaluated against NCI 60-human tumor cell lines. Quinazoline derivatives 5-8, 11, 14, 15, and 17-22 exhibited potential antiproliferative activities with positive cytotoxic effects and median growth inhibition percentage. Among the tested compounds, derivatives 14, 20, and 21 showed the highest activity as antiproliferative agents compared to erlotinib and gefitinib. Quinazolines 5, 14, 18, and 20 demonstrated strong EGFR inhibition activity, while derivatives 9, 14, and 20 showed potent HER2 inhibition activity. Compounds 7, 9, and 14 exhibited the highest inhibitory activity against COX-2.