New Indole‐Based Phenylthiazolyl‐2,4‐dihydropyrazolones as Tubulin polymerization inhibitors: Multicomponent Synthesis, Cytotoxicity Evaluation, and <i>in silico</i> Studies

A facile multicomponent synthesis of new indole-based phenylthiazolyl-dihydropyrazolone hybrids, their structural characterization, biological evaluation, and in silico investigations as anticancer agents are reported. Lead molecule 5 i of the series showed potent activity against MCF-7 breast cancer cells with an IC₅₀ of 3.92±0.01 μM while showing minimal toxicity to normal human lung cells (IC₅₀=69.85±3.95 μM). Further studies show that the compound exhibits antiproliferative activity by inducing apoptosis in MCF-7 cancer cells. The wound healing assay indicated impaired cell migration under the concentration-dependent dosage. The lead molecule 5 i also successfully inhibited the tubulin polymerase enzyme with an IC₅₀ of 4.16±0.18 μM. A flow cytometric assay indicated compound 5 i induced apoptosis through G0 phase cell cycle arrest. The binding mode and interactions of the compound with the tubulin were predicted by molecular modelling and calculating binding free energies. These findings explain the current series as a new class of microtubule polymerization inhibitors with anticancer activity suitable for developing anticancer agents targeting tubulin.