Novel p-carborane-containing multitarget anticancer agents inspired by the metabolism of 17β-estradiol

Publication date: Available online 12 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Asako Kaise, Kiminori Ohta, Yasuyuki Endo
The female hormone 17 β -estradiol (E2) is synthesized from estrone by steroid sulfatase (STS), and metabolized into 2-methoxyestradiol (2-ME), whereby the biological activity of the latter is substantially different from that of E2. Based on the metabolic pathways of E2, a carborane-containing 2-ME mimic (1c) and its derivatives (1 and 2) were designed and synthesized as novel multitarget anticancer agents. Bissulfamate 1f exhibited potent STS-inhibitory activity and tubulin-polymerization-inhibitory activity. Moreover, the cell-growth-inhibitory (CGI) activity of 1f was similar to that of 2-ME in a panel screening against 39 human cancer cell lines. Accordingly, 1f should be a promising perspective therapeutic agent for hormone-dependent breast tissue.

Graphical abstract

http://ift.tt/2ykjJTL