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Novel steroidal 1,3,4-thiadiazines: Synthesis and biological evaluation in androgen receptor-positive prostate cancer 22Rv1 cellsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Komendantova Anna S., Scherbakov Alexander M., Komkov Alexander V., Chertkova Viktoriya V., Gudovanniy Alexey O., Chernoburova Elena I., Sorokin Danila V., Dzichenka Yaraslau U., Shirinian Valerii Z., Volkova Yulia A., Zavarzin Igor V.
- Журнал: Bioorganic Chemistry
- Том: 91
- Год издания: 2019
- Издательство: Academic Press
- Местоположение издательства: United States
- Первая страница: 103142
- DOI: 10.1016/j.bioorg.2019.103142
- Аннотация: A flexible approach to previously unknown spirofused and linked 1,3,4-thiadiazine derivatives of steroids with selective control of heterocyclization patterns is disclosed. (N-Arylcarbamoyl)spiroandrostene-17,6′ [1,3,4]thiadiazines and (N-arylcarbamoyl)17-[1′,3′,4′]thiadiazine-substituted androstenes, novel types of heterosteroids, were prepared from 16β,17β-epoxypregnenolone and 21-bromopregna-5,16-dien-20-one in good to high yields by the treatment with oxamic acid thiohydrazides. The synthesized compounds were screened for antiproliferative activity against the human androgen receptor-positive prostate cancer cell line 22Rv1. Most of (N-arylcarbamoyl)17-[1′,3′,4′]thiadiazine-substituted androstenes exhibit better antiproliferative potency (IC50 = 2.1–6.6 µM) than the antiandrogen bicalutamide. Compounds 7d with IC50 = 3.0 μM and 7j with IC50 = 2.1 μM proved to be the most active in the series under study. Lead synthesized compound 7j downregulates AR expression and activity in 22Rv1 cells. NF-κB activity is also blocked in 7j-treated 22Rv1 cells. Apoptosis is considered as a possible mechanism of 7j-induced cell death.
- Добавил в систему: Гудованный Алексей Олегович