Synthesis of new imidazol derivatives and investigation of aromatase inhibition effects

Aromatase, a cytochrome P450 hemoprotein that is responsible for oestrogen biosynthesis by conversion of androgensint oestrogens, has been an attractive target in the treatment of hormone-dependent breast cancer. The exploration of innovative aromatase inhibitors represents an important approach for the identification of new therapeutic treatments of breast cancer. In this respect, a series of imidazole derivatives was designed, synthesized and were evaluated in vitro on the human breast cancer cell line MCF-7 by MTT assay. In order to determine the selectivity of the compounds, their cytotoxic effects were also investigated on the L929 healthy fibroblast cell line. Compounds 1a, 1b and 1d were found to be more effective than the reference drug cisplatin against the MCF-7 cell line. It is seen that the cytotoxic effects of the compounds on the L929 cell line are quite low and the compounds are found to be highly selective. The inhibition potentials of the 1a, 1b, 1d and 1k coded compounds, which were effective on the MCF-7 cell line, on the aromatase enzyme were evaluated and it was found that the compounds had similar effects with the reference drug letrazole. Further, the interactions between the best active compounds and the active site of the enzyme were analyzed through docking study. The obtained results allow to consider this compounds as an interesting lead for the development of a new class of non-steroidal aromatase inhibitors.