期刊
COORDINATION CHEMISTRY REVIEWS
卷 445, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.ccr.2021.213950
关键词
Anticancer agents; Bidentate bioactive ligands; Bioorganometallics; Metallodrugs; Mode of action; Synergistic activity
资金
- University of Auckland
- Marsden Fund Council
- Cancer Research Trust
- Health Research Council of New Zealand
- Polish National Agency for Academic Exchange for a Bekker Scholarship [PPN/BEK/2018/1/00492]
The article discusses strategies to enhance the activity and reduce the side effects of metal-based drugs, as well as how these strategies can be applied to half-sandwich organoruthenium anticancer compounds.
The small molecule anticancer agent cisplatin and its Pt(II) analogs carboplatin and oxaliplatin are widely used to treat a variety of tumorigenic diseases. Despite their structural simplicity, side effects and disadvantages, they are cornerstones of cancer chemotherapy. Several strategies have been pursued to enhance the activity and reduce the side effects of metal-based drugs, for example, to use bioactive ligands that equip them with novel modes of action, enhance delivery, allow for selective activation, create synergistic effects or improve tumor accumulation. Many of these strategies have been developed for or adapted in the design of half-sandwich organoruthenium compounds. For such compounds decorated with bioactive ligands that coordinate monodentately to the Ru center, we have identified five design concepts (Coord. Chem. Rev. 2021, 439, 213890): (i) the bioactive ligand coordinates directly to the Ru center or (ii) after functionalization with a coordinating group, (iii) the ligand(s) and the Ru center solely define the overall shape of the molecule, (iv) the bioactive ligand is released, and (v) the bioactive ligand acts as a vector to the tumor (cell). Herein, we use these five concepts and explore their application to half-sandwich organoruthenium anticancer compounds in which the bioactive ligand is coordinated to the Ru center through a bidentate chelating motif. (C) 2021 Elsevier B.V. All rights reserved.
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