Discovery of pyrazole derivatives as promising leads against NSCLC: An integrated computational and experimental...

Lung cancer remains a leading cause of cancer-related mortality worldwide, with non-small cell lung carcinoma (NSCLC) representing the predominant subtype. Despite advances in targeted therapies, the development of potent and selective small-molecule therapeutics for NSCLC remains a key challenge in drug discovery. In this study, we designed and computationally evaluated a focused library of pyrazole-based derivatives as potential anticancer agents. A rational, multi-step in silico workflow integrating target prediction, molecular docking, and drug-likeness assessment was employed to identify promising candidates. Twelve pyrazole derivatives were docked against multiple NSCLC-relevant protein kinases, and their ADME properties were predicted using SwissADME webserver. Among these, PL-13 emerged as a lead candidate and was subsequently synthesized, structurally characterized, and evaluated in vitro. Cytotoxicity studies using the MTT assay demonstrated that PL-13 exhibits potent antiproliferative activity against A549 NSCLC cells while maintaining favorable selectivity over non-cancerous HFL-1 fibroblasts. These findings highlight pyrazole-based scaffolds as promising leads for NSCLC drug discovery and establish PL-13 as a valuable starting point for further SAR-driven optimization.