Synthesis of Novel 2-(Isopropylamino)thiazol-4(5H)-one Derivatives and Their Inhibitory Activity of 11β-HSD1 and 11β-HSD2 in Aspect of Carcinogenesis Prevention
2020
Daria Kupczyk | Renata Studzińska | Rafał Bilski | Szymon Baumgart | Renata Kołodziejska | Alina Woźniak
Glucocorticoid metabolism at the tissue level is regulated by two isoenzymes 11&beta:-hydroxysteroid dehydrogenase (11&beta:-HSD), which mutually convert biologically active cortisol and inactive cortisone. Recent research is focused on the role of 11&beta:-HSD1 and 11&beta:-HSD2 as autocrine factors of tumor cell proliferation and differentiation. Herein, we report the synthesis of novel 2-(isopropylamino)thiazol-4(5H)-one derivatives and their inhibitory activity for 11&beta:-HSD1 and 11&beta:-HSD2. The derivative containing the spiro system of thiazole and cyclohexane rings shows the highest degree of 11&beta:-HSD1 inhibition (54.53% at 10 µ:M) and is the most selective inhibitor of this enzyme among the tested compounds. In turn, derivatives containing ethyl and n-propyl group at C-5 of thiazole ring inhibit the activity of 11&beta:-HSD2 to a high degree (47.08 and 54.59% at 10 µ:M respectively) and are completely selective. Inhibition of the activity of these enzymes may have a significant impact on the process of formation and course of tumors. Therefore, these compounds can be considered as potential pharmaceuticals supporting anti-cancer therapy.
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