Secosteroid thiosemicarbazides and secosteroid–1,2,4-triazoles as antiproliferative agents targeting breast cancer cells: Synthesis and biological evaluation

A convenient and selective approach to 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N’-arylcarbothioamido]hydrazides and hybrid molecules containing secosteroid and 1,2,4-triazole fragments was disclosed and these novel types of secosteroids were screened for cytotoxicity against hormone-dependent h...

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Bibliographic Details
Published in:	The Journal of steroid biochemistry and molecular biology Vol. 234; p. 106386
Main Authors:	Ilovaisky, Alexey I., Scherbakov, Alexander M., Chernoburova, Elena I., Povarov, Andrey A., Shchetinina, Marina A., Merkulova, Valentina M., Salnikova, Diana I., Sorokin, Danila V., Bozhenko, Eugene I., Zavarzin, Igor V., Terent’ev, Alexander O.
Format:	Journal Article
Language:	English
Published:	Elsevier Ltd 01-11-2023
Subjects:	4-Triazoles Breast cancer Cytotoxicity Hydrazides Secosteroids Thiosemicarbazides Secosteroids 1 4-Triazoles 2 Cytotoxicity Breast cancer Hydrazides Thiosemicarbazides
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Summary:	A convenient and selective approach to 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N’-arylcarbothioamido]hydrazides and hybrid molecules containing secosteroid and 1,2,4-triazole fragments was disclosed and these novel types of secosteroids were screened for cytotoxicity against hormone-dependent human breast cancer cell line MCF-7. Most of secosteroid–1,2,4-triazole hybrids showed significant cytotoxic effect comparable or superior to that of the reference drug cisplatin. Hit secosteroid–1,2,4-triazole hybrids 4b and 4h were characterized by high cytotoxicity and good selectivity towards MCF-7 breast cancer cells. PARP cleavage (marker of apoptosis) and ERα and cyclin D1 downregulation were discovered in MCF-7 cells treated with lead secosteroid–1,2,4-triazole hybrid 4b. The synthesized secosteroids may be considered as new promising anticancer agents. [Display omitted] •Secosteroid thiosemicarbazides and secosteroid–1,2,4-triazoles were synthesized.•A number of obtained compounds showed good cytotoxicity for MCF-7 cancer cells.•Hit compounds 4b and 4h superior to the reference drug cisplatin.•Hit compound 4b caused PARP cleavage and ERα and cyclin D1 downregulation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-0760 1879-1220
DOI:	10.1016/j.jsbmb.2023.106386