Abstract
A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determined to be the most potent compound. Tubulin polymerization and immunostaining experiments revealed that 10s potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Moreover, 10s effectively induced SGC-7901 cell cycle arrest at the G2/M phase in both concentration- and time-dependent manners. The molecular docking results revealed that 10s could bind to the colchicine binding site of tubulin.
Highlights
Microtubules are key structural components in eukaryotic cells and play a crucial role in a number of cellular functions, including regulation of motility, cell division, organelle transport, maintenance of cell morphology and signal transduction [1,2]
Given the success of paclitaxel and vinblastine, research efforts have been focused on developing colchicine binding site inhibitors (CBSIs) for cancer treatment, and a number of effective CBSIs are currently being investigated in clinical studies [7]
The compound 10u was obtained by a simple reaction of the compound 10s with methyl iodide in anhydrous DMF, and the compound 10v was obtained by an acetylation reaction of compound 10s with acetic anhydride
Summary
Microtubules are key structural components in eukaryotic cells and play a crucial role in a number of cellular functions, including regulation of motility, cell division, organelle transport, maintenance of cell morphology and signal transduction [1,2]. To evaluate the ability of various 2-aminothiazole derivatives to inhibit cancer cell growth, the target compounds 10a-v, reference compounds CA-4 (2), nocodazole (3) and SMART (5) were screened for antiproliferative activity in three human cancer cell lines using a standard MTT assay (Table 2).
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