Synthesis and antiproliferative evaluation of some novel estradiol selenocyanates

Selenocyano fragments with different structural characteristics have been successfully installed into the 3- and 17-position of estradiol through the etherification and esterification of its 3 or 17-hydroxyl group respectively. A total of 12 new estradiol selenocyanates were synthesized and their structures were characterized by NMR and HRMS. The tumor cell lines related to the expression of human hormones were selected as the screening objects, and the antiproliferative activity of the target compounds was further investigated. The results showed that the introduction of selenocyano group in estradiol could endue estradiol with the activity of inhibiting tumor cell proliferation, and 3-selenocyanoalkyl estradiol ethers had stronger cytotoxicity than their 17-selenocyanocarboxylates counterpart. Among them, IC₅₀ value of compound 3e on HeLa cells was 5.69 μM. The information obtained from the studies may be useful for the design and development of novel chemotherapeutic drugs.