Colorectal cancer (CRC) remains a major global health challenge, with current therapeutic options often limited by drug resistance and adverse effects. Small molecules provide distinct advantages, including oral bioavailability, cost‐effectiveness, and the ability to target intracellular pathways critical for tumor progression. In this study, we designed and synthesized a new series of pyrazolone derivatives with varied substitution patterns using microwave‐assisted methods and evaluated their antiproliferative activity against CRC cell lines (HCT‐116 and WiDr). Among these, PL‐13 emerged as a potent and selective candidate, exhibiting strong cytotoxicity toward cancer cells while sparing noncancerous CRL‐1459 colon cells. Functional assays, including colony formation and wound healing, confirmed its ability to inhibit cell proliferation and migration. Western blot analyses demonstrated that PL‐13 induces apoptosis via the intrinsic mitochondrial pathway, as evidenced by increased levels of cleaved caspase‐9 and PARP, and modulates LC3A/B expression, suggesting involvement of autophagy. Kinome profiling revealed selective binding of PL‐13 to FLT3, which was validated by an IC 50 value of 8.2 μM. Molecular docking further supported these findings, showing favorable binding energy (–7.98 kcal/mol) compared to regorafenib (–7.13 kcal/mol). Collectively, these results highlight PL‐13 as a promising lead compound for further optimization toward CRC therapy.
Moghaddam et al. (Thu,) studied this question.