Design and synthesis of p-carborane-containing sulfamates as multitarget anti-breast cancer agents

Publication date: Available online 16 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Asako Kaise, Kiminori Ohta, Chinami Shirata, Yasuyuki Endo
The development of multitarget anticancer agents is of high interest to medicinal chemists in terms of overcoming drug resistance and preventing cancer-cell migration. Based on the structure of the potent carborane-containing estrogen BE120, non-steroidal multitarget anti-breast cancer agent candidates 1a–1j were designed and synthesized. Compound 1f shows potent STS-inhibitory activity (IC50 = 1.8 μM), cell-growth-inhibitory (CGI) activity against 39 human cancer cell lines (MG-MID = 2.8 μM), and tubulin-polymerization-inhibitory (TPI) activity. An analysis of the DNA content for MDA-MB-453 breast cancer cells revealed that 1f arrests the cell cycle in the G2/M phase and induces apoptosis. Accordingly, 1f should be a promising therapeutic agent for hormone-dependent breast cancer.

Graphical abstract

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