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

  • J Med Chem. 2017 Oct 26;60(20):8661-8666. doi: 10.1021/acs.jmedchem.7b00701.
Tristan Rawling  1 ,  Hassan Choucair  2 ,  Nooshin Koolaji  2 ,  Kirsi Bourget  2 ,  Sarah E Allison  2 ,  Yong-Juan Chen  3 ,  Colin R Dunstan  3 ,  Michael Murray  2
Affiliations
  • 1. School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney , Ultimo, New South Wales 2007, Australia.
  • 2. Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney , Sydney, New South Wales 2006, Australia.
  • 3. School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney , Sydney, New South Wales 2006, Australia.
PMID: 28921987 DOI: 10.1021/acs.jmedchem.7b00701
Abstract

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.

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