Novel steroidal 1,3,4-thiadiazines: Synthesis and biological evaluation in androgen receptor-positive prostate cancer 22Rv1 cells

Novel steroidal 1,3,4-thiadiazines: Synthesis and biological evaluation in androgen receptor-positive prostate cancer 22Rv1 cells Full article

Journal

Bioorganic Chemistry
ISSN: 1090-2120 , E-ISSN: 0045-2068

Output data

Year: 2019, Volume: 91, Article number : 103142, Pages count : DOI: 10.1016/j.bioorg.2019.103142

Authors

Komendantova Anna S. ¹ , Scherbakov Alexander M. ² , Komkov Alexander V. ¹ , Chertkova Viktoriya V. ¹ , Gudovanniy Alexey O. ¹ , Chernoburova Elena I. ¹ , Sorokin Danila V. ² , Dzichenka Yaraslau U. ³ , Shirinian Valerii Z. ¹ , Volkova Yulia A. ¹ , Zavarzin Igor V. ¹

Affiliations

1	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., 119991 Moscow, Russia
2	Department of Experimental Tumor Biology, N.N. Blokhin National Medical Research Center of Oncology, 24 Kashirskoe Shosse, 115522 Moscow, Russia
3	Institute of Bioorganic Chemistry of NAS of Belarus, Laboratory of Protein Engineering, Academician V.F. Kuprevich Str. 5/2, Minsk, Belarus

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.

Komendantova A.S. , Scherbakov A.M. , Komkov A.V. , Chertkova V.V. , Gudovanniy A.O. , Chernoburova E.I. , Sorokin D.V. , Dzichenka Y.U. , Shirinian V.Z. , Volkova Y.A. , Zavarzin I.V.
Novel steroidal 1,3,4-thiadiazines: Synthesis and biological evaluation in androgen receptor-positive prostate cancer 22Rv1 cells
Bioorganic Chemistry. 2019. V.91. 103142 . DOI: 10.1016/j.bioorg.2019.103142 WOS Scopus OpenAlex

Web of science:	WOS:000487812000039
Scopus:	2-s2.0-85070209453
OpenAlex:	W2963913257

DB	Citing
OpenAlex	36
Scopus	36
Web of science	32