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

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.