Secosteroid diacylhydrazines as novel effective agents against hormone-dependent breast cancer cells

Secosteroid diacylhydrazines as novel effective agents against hormone-dependent breast cancer cells Full article

Journal

The Journal of Steroid Biochemistry and Molecular Biology
ISSN: 1879-1220 , E-ISSN: 0960-0760

Output data

Year: 2024, Volume: 244, Article number : 106597, Pages count : DOI: 10.1016/j.jsbmb.2024.106597

Authors

Ilovaisky Alexey I ¹ , Scherbakov Alexander M ^2,3 , Chernoburova Elena I ¹ , Shchetinina Marina A ¹ , Merkulova Valentina M ¹ , Bogdanov Fedor B ² , Sorokin Danila V ² , Salnikova Diana I ^1,2 , Bozhenko Eugene I ¹ , Zavarzin Igor V ¹ , Terent'ev Alexander O ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, Moscow 119991, Russia.
2	N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115522, Russia; Gause Institute of New Antibiotics, Bol'shaya Pirogovskaya ulitsa 11, Moscow 119021, Russia.
3	Gause Institute of New Antibiotics, Bol’shaya Pirogovskaya ulitsa 11, Moscow 119021, Russia

This research aimed to develop novel selective secosteroids that are highly active against hormone-dependent breast cancer. A simple and convenient approach to N′-acylated 13,17-secoestra-1,3,5(10)-trien-17-oic acid hydrazides was disclosed and these novel types of secosteroids were screened for cytotoxicity against the hormone-dependent human breast cancer cell line MCF7. Most secosteroid N′-benzoyl hydrazides have demonstrated high cytotoxicity against MCF7 cells with IC50 values below 5 μM, which are superior to that of the reference drug cisplatin. Hit compounds 2c, 2e and 2i were characterized by high cytotoxicity (IC50 = 1.6–1.9 μM) and very good selectivity towards MCF7 breast cancer cells. The lead secosteroids 2c, 2e and 2i also exhibit antiestrogenic effects and alter the expression of cell cycle regulating proteins. The effect of selected compounds on PARP (poly(ADP-ribose) polymerase) and Bcl-2 (B-cell CLL/lymphoma 2) indicates their proapoptotic potential. The synthesized secosteroids may be considered as new promising anti-breast cancer agents targeting ERα and apoptosis pathways.

Ilovaisky A.I. , Scherbakov A.M. , Chernoburova E.I. , Shchetinina M.A. , Merkulova V.M. , Bogdanov F.B. , Sorokin D.V. , Salnikova D.I. , Bozhenko E.I. , Zavarzin I.V. , Terent'ev A.O.
Secosteroid diacylhydrazines as novel effective agents against hormone-dependent breast cancer cells
The Journal of Steroid Biochemistry and Molecular Biology. 2024. V.244. 106597 . DOI: 10.1016/j.jsbmb.2024.106597 Scopus OpenAlex

Scopus:	2-s2.0-85200810981
OpenAlex:	W4401422647

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