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

Background: 4-Methylacetophenone is used in the preparation of starting materials, 4-methylphenacyle bromide (2) and 4-methylacetophenone thiosemicarbazole (3). Results: 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 5–8 respectively. Conclusion: Compounds 5–8 were investigated for their cytotoxic activity on MCF-7 and normal breast cells. Active compounds were found and in contrast to staurosporine, compound 8 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 8 and the binding pocket of the tyrosine kinase and aromatase protein receptors showed the hydrophilic and hydrophobic interactions of compound 8.
Thiazole derivatives were investigated for their cytotoxic activity on MCF-7 in vitro and normal breast cells.
Our synthetic route led to the formation of 4-methylphenacyl bromide (2) and 4-methylacetophenone thiosemicarbazone (3).
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 8 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.