Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots

Chem Sci. 2019 May 22;10(23):5884-5892. doi: 10.1039/c9sc01218d. eCollection 2019 Jun 21.

Abstract

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.