Journal
CHEMICAL SCIENCE
Volume 10, Issue 23, Pages 5884-5892Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9sc01218d
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Funding
- New York University Abu Dhabi (NYUAD), UAE
- Al Jalila Foundation [AJF 201646]
- New York University Abu Dhabi
- National Institute of Health [NIH 5R01AA018886]
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A set of metal-organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells--including those resistant to cisplatin--and in zebrafish embryos. In cultured cells, M-TKs generated reactive oxygen species that triggered apoptosis via the mitochondrial pathway without directly disrupting the cell-membrane or damaging nuclear DNA. The cytotoxicity and wide scope for structural variation of M-TKs indicate the potential of synthetic metal-organic knots as a new field of chemical space for pharmaceutical design and development.
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