Secosteroid – 1,3,4-Oxadiazole Hybrids: Synthesis and Evaluation of Their Activity Against Hormone-Dependent Breast Cancer Cells

Secosteroid – 1,3,4-Oxadiazole Hybrids: Synthesis and Evaluation of Their Activity 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: 2025, Volume: 251, Article number : 106745, Pages count : DOI: 10.1016/j.jsbmb.2025.106745

Authors

Ilovaisky Alexey I ¹ , Scherbakov Alexander M ^2,3 , Miciurov Dumitru ¹ , Chernoburova Elena I ¹ , Merkulova Valentina M ¹ , Bogdanov Fedor B ² , Salnikova Diana I ² , Sorokin Danila V ² , Krasil'nikov Mikhail A 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
3	Gause Institute of New Antibiotics, Bol’shaya Pirogovskaya ulitsa 11, Moscow 119021, Russia

This study focused on the synthesis of secosteroids with good antiproliferative properties against hormone-dependent breast cancer. A straightforward and efficient method for synthesizing secosteroid – 1,3,4-oxadiazole hybrids was developed starting from 13α-hydroxy-3-methoxy-13,17-secoestra-1,3,5(10)-trien-17-oic acid hydrazide. The cyclization of hydrazide moiety with CS2 into 1,3,4-oxadiazole-2(3H)-thione fragment followed by sulfur alkylation resulted in the formation of various secosteroid – 2-mercapto-1,3,4-oxadiazole hybrids. These novel compounds were evaluated for their antiproliferative activity against the hormone-dependent human breast cancer cell line MCF-7. Among the synthesized hybrids, compounds 3i, 3o, and 3q displayed notable antiproliferative effects, with IC50 values ranging from 6.5 to 8.9 µM, comparable to the reference drug cisplatin. Furthermore, compound 3i showed minimal toxicity toward non-cancerous hFB-hTERT fibroblasts, indicating high selectivity. Compounds 3o and 3q exhibited antiestrogenic activity. Additionally, their effects on PARP and Bcl-2 suggest a pro-apoptotic mechanism of action. These findings highlight the potential of secosteroidal hybrids as promising candidates for the development of new anti-breast cancer agents targeting ERα and apoptosis pathways.

Ilovaisky A.I. , Scherbakov A.M. , Miciurov D. , Chernoburova E.I. , Merkulova V.M. , Bogdanov F.B. , Salnikova D.I. , Sorokin D.V. , Krasil'nikov M.A. , Bozhenko E.I. , Zavarzin I.V. , Terent'ev A.O.
Secosteroid – 1,3,4-Oxadiazole Hybrids: Synthesis and Evaluation of Their Activity Against Hormone-Dependent Breast Cancer Cells
The Journal of Steroid Biochemistry and Molecular Biology. 2025. V.251. 106745 . DOI: 10.1016/j.jsbmb.2025.106745 OpenAlex

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