A Novel Arylurea Fatty Acid That Targets the Mitochondrion and Depletes Cardiolipin To Promote Killing of Breast Cancer Cells

作者：Rawling Tristan^*; Choucair Hassan; Koolaji Nooshin; Bourget Kirsi; Allison Sarah E; Chen Yong Juan; Dunstan Colin R; Murray Michael

来源：Journal of Medicinal Chemistry, 2017, 60(20): 8661-8666.

DOI：10.1021/acs.jmedchem.7b00701

Cancer cell mitochondria are promising anticancer drug targets because they control cell death and are structurally and functionally different from normal cell mitochondria. We synthesized arylurea fatty acids and found that the analogue 16-({[4-chloro-3-(trifluoromethyl)-phenyl]carbamoyl}amino)hexadecanoic acid (13b) decreased proliferation and activated apoptosis in MDA-MB-231 breast cancer cells in vitro and in vivo. In mechanistic studies 13b emerged as the prototype of a novel class of mitochondrion-targeted agents that deplete cardiolipin and promote cancer cell death.

• 出版日期2017-10-26