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

Chemical Science
Farah BenyettouAli Trabolsi

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.

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Citations

Nov 2, 2019·Chemistry : a European Journal·Kenji CapriceTatu Kumpulainen
Aug 5, 2020·Nature Chemistry·Nathalie KatsonisFredrik Schaufelberger
Dec 19, 2020·Frontiers in Chemistry·Cristina Belda MarínChristophe Egles
Dec 16, 2020·Nature Chemistry·David A LeighSteffen L Woltering
Aug 10, 2021·Supramolecular Chemistry·Kimberly G BradyLyle Isaacs
Jul 15, 2020·Nano Letters·J Fraser Stoddart
Oct 22, 2020·Journal of the American Chemical Society·David P AugustSimon J Webb
Oct 23, 2020·Journal of the American Chemical Society·Farah BenyettouAli Trabolsi
Aug 8, 2019·Journal of the American Chemical Society·Jiankang ZhongDavid A Leigh

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Methods Mentioned

BETA
X-ray
FACS
flow cytometry

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