Mitochondrially targeted anti-cancer agents.
Cancer is an ever-increasing problem that is yet to be harnessed. Frequent mutations make this pathology very variable and, consequently, a considerable challenge. Intriguingly, mitochondria have recently emerged as novel targets for cancer therapy. A group of agents with anti-cancer activity that induce apoptosis by way of mitochondrial destabilisation, termed mitocans, have been a recent focus of research. Of these compounds, many are hydrophobic agents that associate with various sub-cellular organelles. Clearly, modification of such structures with mitochondria-targeting moieties, for example tagging them with lipophilic cations, would be expected to enhance their activity. This may be accomplished by the addition of triphenylphosphonium groups that direct such compounds to mitochondria, enhancing their activity. In this paper, we will review agents that possess anti-cancer activity by way of destabilizing mitochondria and their possible targets. We propose that mitochondrial targeting, in particular where the agent associates directly with the target, results in more specific and efficient anti-cancer drugs of potential high clinical relevance.
Biasutto
Lucia
L
CNR Institute of Neuroscience and Dept. of Experimental Biomedical Sciences, University of Padova, Padova, Italy.
Dong
Lan-Feng
LF
Zoratti
Mario
M
Neuzil
Jiri
J
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents