Secosteroidal hydrazides: Promising scaffolds for anti-breast cancer agents

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 214; p. 106000
• Main Authors: Ilovaisky, Alexey I., Merkulova, Valentina M., Chernoburova, Elena I., Shchetinina, Marina A., Salnikova, Diana I., Scherbakov, Alexander M., Zavarzin, Igor V., Terent’ev, Alexander O.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2021; Elsevier BV
• Subjects: Anti-Bacterial Agents - pharmacology; Antineoplastic Agents - pharmacology; Antitumor agents; Azomethines; Breast - drug effects; Breast cancer; Breast Neoplasms - drug therapy; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Pharmaceutical - methods; Cisplatin; Cytotoxicity; D-Secosteroids; Drug Design; Drug Screening Assays, Antitumor; Female; Humans; Hydrazides; Hydrazines - chemistry; Inhibitory Concentration 50; Lactones - chemistry; Magnetic Resonance Spectroscopy; MCF-7 Cells; Molecular Structure; Steroidal lactones; Steroids - chemistry; Structure-Activity Relationship; Cytotoxicity; Steroidal lactones; Breast cancer; D-Secosteroids; Hydrazides; Azomethines
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2021.106000

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•A selective approach to antitumor agents based on the opening of ring D in steroidal lactones by hydrazines was developed.•Secosteroidal [N’-(het)arylmethylene]hydrazides are proved to be active towards MCF-7 breast cancer cells.•Hit compounds showed high cytotoxicity for MCF-7 breast cancer cells and rather low toxicity towards MCF-10A normal cells.
A convenient and selective approach to 13,17-secoestra-1,3,5(10)-trien-17-oic acid hydrazides and their N’-(het)arylmethylene derivatives was disclosed and these novel types of secosteroids were screened for cytotoxicity against hormone-dependent human breast cancer cell line MCF-7. A number of 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N’-(het)arylmethylene]hydrazides show significant cytotoxic effect comparable or superior to that for reference drug cisplatin. Compound 3l exhibits the highest activity with the IC50 value of about 2 μM and is 2.8 times more active than cisplatin. Hit 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N’-(het)arylmethylene]hydrazides 3d, 3l and 3q are characterized by high cytotoxicity and good selectivity towards MCF-7 breast cancer cells. The synthesized secosteroids may be considered as new promising antitumor agents.