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

Amruta Jayant Waichal; Moreshwar Prafulla Mahajan

doi:10.22146/ijc.114148

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

https://doi.org/10.22146/ijc.114148

Amruta Jayant Waichal^(1*), Moreshwar Prafulla Mahajan⁽²⁾

(1) Sinhgad Technical Education Society’s, Sinhgad Institute of Pharmacy, Opp. Kashibai Navale Hospital, Narhe, Pune, Maharashtra, 411041. Affiliated to Savitribai Phule Pune University, Pune, Maharashtra 411007, India
(2) Sinhgad Technical Education Society’s, Sinhgad Institute of Pharmacy, Opp. Kashibai Navale Hospital, Narhe, Pune, Maharashtra, 411041. Affiliated to Savitribai Phule Pune University, Pune, Maharashtra 411007, India
(*) Corresponding Author

Abstract

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.

Keywords

synthesis; characterization; anticancer; thiazole; tubulin polymerization

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DOI: https://doi.org/10.22146/ijc.114148