Yeni bazı tiyazolinon türevlerinin sentezi ve aromataz enzimi üzerine etkilerinin incelenmesi

Aromatase enzyme is an essential cytochrome P450 subtype. It is responsible for the rate-limiting steps in the biosynthesis of estrogen from androgen in human being and the synthesis of ergosterol from lanosterol in fungi by the (CYP19A1) and (CYP51) subtypes, respectively. Aromatase inhibitors interfere with these synthetic steps. Thus, they have been used for postmenopausal women with estrogen dependent breast cancer. However, hormonal therapy of estrogen-responsive malignancy has been used to prolong the disease-free time in females and to improve their quality of life. AIs additionally interfere with ergosterol biosynthesis, an essential part of the fungal cell membrane this explaining the usage of AIs as an antifungal agent. Although scientists have been focusing on finding a radical cure for these diseases, the emergence of resistance, and the side effects associated with drugs available in the market, boost the need for new selective non-steroidal AIs. Inspired by the previously mentioned facts and by using our practical information on rational drug design and synthesis, a series of new benzothiazole-based thiazolinone derivatives were synthesized and their structures were elucidated and confirmed by analytical methods. In general, the aims of our study were achieved, and the synthesized derivatives showed inhibition to aromatase enzyme. Compound 3b is the most active analog with IC50 0.041±0.002 (µM) and letrozole drug used as positive control. The compound 3i showed inhibition by more than 70% at 10-3M. The in silico studies were used to determine the possible interaction mode of the compound 3b and receptor. The findings from this study will participate positively in discovering new, potent, and selective third generation NSAIs and will support future research on aromatase enzymes.