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 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.