Design and evaluation of some new tetra substituted pyrrole derivatives as potential anticancer against K562 and HeLa cells

We report the design and synthesis of a new series of tetrasubstituted pyrrole analogues and their systematic evaluation for antiproliferative activity against human cancer cell lines. The synthesized pyrrole derivatives displayed broad-spectrum anticancer activity, among which diethyl-4-(4-chlorophenyl)-1-(3-methoxybenzyl)-1H-pyrrole-2,3-dicarboxylate (15c) emerged as the most potent candidate, exhibiting IC₅₀ values of 23.21 μM against K562 leukemia cells and 32.74 μM against HeLa cervical cancer cells. Mechanistic investigations revealed that compound 15c induces significant cell-cycle arrest and mitochondrial membrane depolarization, confirming its pronounced antiproliferative efficacy. The molecule 15c exhibits a HOMO–LUMO energy gap of 4.5859 eV, and its energy distribution and chemically reactive regions were mapped using an electrostatic potential surface. Docking studies demonstrated a favorable binding interaction of compound 15c with MAP kinase p38, while molecular dynamics simulations confirmed the ligand firmly binds to protein complex throughout the simulation period. Notably, the in vitro antiproliferative activity correlated well with the in silico predictions, highlighting compound 15c as a promising lead for further anticancer drug development.