Synthesis of Novel 2-(Isopropylamino)thiazol-4(5H)-one Derivatives and Their Inhibitory Activity of 11?-HSD1 and 11?-HSD2 in Aspect of Carcinogenesis Prevention.

ABSTRACT: Glucocorticoid metabolism at the tissue level is regulated by two isoenzymes 11?-hydroxysteroid dehydrogenase (11?-HSD), which mutually convert biologically active cortisol and inactive cortisone. Recent research is focused on the role of 11?-HSD1 and 11?-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?-HSD1 and 11?-HSD2. The derivative containing the spiro system of thiazole and cyclohexane rings shows the highest degree of 11?-HSD1 inhibition (54.53% at 10 µM) 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?-HSD2 to a high degree (47.08 and 54.59% at 10 µM 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.

SUBMITTER: Kupczyk D 

PROVIDER: S-EPMC7570983 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature