2-Difluoromethoxy-Substituted Estratriene Sulfamates: Synthesis, Antiproliferative SAR, Antitubulin Activity, and Steroid Sulfatase Inhibition.

ABSTRACT: 2-Difluoromethoxyestratriene derivatives were designed to improve potency and in vivo stability of the drug candidate 2-methoxyestradiol (2ME2). Compound evaluation in vitro against the proliferation of MCF-7 and MDA MB-231 breast cancer cells, as inhibitors of tubulin polymerisation and also steroid sulfatase (STS) both in cell lysates and in whole cells, showed promising activities. In antiproliferative assays 2-difluoromethoxyestradiol was less potent than 2ME2, but its sulfamates were often more potent than their corresponding non-fluorinated analogues. The fluorinated bis-sulfamate is a promising antiproliferative agent in MCF-7 cells (GI₅₀ 0.28 μM) vs the known 2-methoxyestradiol-3,17-O,O-bissulfamate (STX140, GI₅₀ 0.52 μM), confirming the utility of our approac

SUBMITTER: Dohle W 

PROVIDER: S-EPMC9742152 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature