Mitochondrially targeted anti-cancer agents |
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Authors: | Lucia Biasutto Lan-Feng Dong Mario Zoratti Jiri Neuzil |
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Affiliation: | 1. CNR Institute of Neuroscience and Dept. of Experimental Biomedical Sciences, University of Padova, Padova, Italy;2. School of Medical Science, Griffith University, Southport, Qld, Australia;3. Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic;1. Laboratory of Molecular Oncology, Quilmes National University, Roque Saenz Peña 352, Bernal CP1876, Buenos Aires, Argentina;2. Research Area, Institute of Oncology “Angel H. Roffo”, University of Buenos Aires, Av. San Martín 5481, C1417DTB, Buenos Aires, Argentina;3. Laboratory of Molecular Oncology, Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), La Havana, CP10600, PO Box 6162, Cuba;1. State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237, PR China;2. Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, PR China;3. Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road II, Shanghai 200025, PR China;1. Department of Respiratory Medicine, Binzhou Medical University Hospital, Binzhou, 256603, China;2. CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China;3. Institute of Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, China;4. Medicine Research Center, Institute of Molecular Medicine, Binzhou Medical University, Yantai, 264003, China;5. College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, China;1. Computer-Aided Drug Design Lab, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad 500078, A.P., India;2. Incozen Therapeutics Private Limited, Spectrum Discovery Zone, Alexandria Knowledge Park, Phase-I, Shameerpet, Hyderabad 500078, A.P., India;1. Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy;2. Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy;3. Dipartimento di Medicina Molecolare, Università degli Studi di Padova, Via Gabelli 63, 35121 Padova, Italy;1. Center of Bio & Micro/Nano Functional Materials, State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, PR China;2. School of Information Science and Engineering, Shandong University, Jinan 250100, PR China;3. Department of Anatomy, Shandong University School of Medicine, Jinan 250012, PR China |
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Abstract: | 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 destabilising 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. |
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