Design, Synthesis, In Silico Binding Analysis, and Anticancer Evaluation of Novel Thiazole Derivatives

A novel thiazole-based derivative (C1–C5) incorporating amide linkages was designed and synthesized by integrating the bioactive 3,4,5-trimethoxyphenyl and 2-aminothiazole scaffolds. The structural features of the compounds were confirmed by 1H-, 13C-NMR, and mass spectrometry. Computational docking studies against the CBS of tubulin revealed favorable binding affinities for C3 and C4, surpassing those of the reference compound CA-4. The MTT assays were used to test how well they could fight cancer by using the MCF-7 breast cancer cell line, with tamoxifen as the standard drug. Among the synthesized molecules, C1 and C3 exhibited the most potent cytotoxicity, reducing cell viability to 70–40%. The SAR analysis indicated that acyl substituents, particularly NO2 and CF3 groups, enhance cytotoxicity. Moreover, PASS prediction analysis indicated low to moderate toxicity risks, supporting the preliminary safety assessment of these compounds. Collectively, the results indicate that the synthesized thiazole derivatives serve as promising molecular scaffolds for the design of potent tubulin polymerization inhibitors with potential anticancer applications.