Evaluation of novel synthesized thiazole derivatives as potential aromatase inhibitors against breast cancer

<b>Background:</b> 4-Methylacetophenone is used in the preparation of starting materials, 4-methylphenacyle bromide (<b>2</b>) and 4-methylacetophenone thiosemicarbazole (<b>3</b>). <b>Results:</b> Several novel 2,4-disubstituted-1,3-thiazole analogues were obtained via the treatment of starting materials with 4-methylphenacyl bromide, acetyl chloride, aromatic aldehydes and bromination providing thiazole derivatives <b>5–8</b> respectively. <b>Conclusion:</b> Compounds <b>5–8</b> were investigated for their cytotoxic activity on MCF-7 and normal breast cells. Active compounds were found and in contrast to staurosporine, compound <b>8</b> displayed the most potent cytotoxic action that showed a strong inhibitory effect (aromatase) and (protein tyrosine kinase) enzymes, proving that the novel thiazole derivatives promoted the effective anticancer drug candidates. In this study, a docking simulation investigation between compound <b>8</b> and the binding pocket of the tyrosine kinase and aromatase protein receptors showed the hydrophilic and hydrophobic interactions of compound <b>8</b>. Thiazole derivatives were investigated for their cytotoxic activity on MCF-7 <i>in vitro</i> and normal breast cells. Our synthetic route led to the formation of 4-methylphenacyl bromide (<b>2</b>) and 4-methylacetophenone thiosemicarbazone (<b>3</b>). The majority of the compounds examined demonstrated strong anti-breast cancer effects and IC₅₀ values between 3.36 and 6.09 μg/ml showing higher activity than the reference drug staurosporine (5.25 μg/ml). The target compound <b>8</b> induced apoptosis in the pre-G1 phase and halted the cell cycle in the G1 and S phases. As the compounds retained their activity against breast cancer cell lines with IC₅₀, this could be a starting point for further development toward new anticancers.