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- Title
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.
- Authors
Kupczyk, Daria; Studzińska, Renata; Bilski, Rafał; Baumgart, Szymon; Kołodziejska, Renata; Woźniak, Alina; Tylkowski, Bartosz; Bajek, Anna; Roszkowski, Krzysztof
- Abstract
Glucocorticoid metabolism at the tissue level is regulated by two isoenzymes 11β-hydroxysteroid dehydrogenase (11β-HSD), which mutually convert biologically active cortisol and inactive cortisone. Recent research is focused on the role of 11β-HSD1 and 11β-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 11β-HSD1 and 11β-HSD2. The derivative containing the spiro system of thiazole and cyclohexane rings shows the highest degree of 11β-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 11β-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.
- Subjects
CORTISONE; INHIBITION (Chemistry); CARCINOGENESIS; ETHYL group; TISSUE metabolism; CELL proliferation
- Publication
Molecules, 2020, Vol 25, Issue 18, p4233
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25184233