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

Farah Benyettou, Thirumurugan Prakasam, Anjana Ramdas Nair, Ini Isabee Witzel, Marwa Alhashimi, Tina Skorjanc, John Carl Olsen, Kirsten C. Sadler, Ali Trabolsi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5884-5892
Number of pages9
JournalChemical Science
Volume10
Issue number23
DOIs
StatePublished - Jun 21 2019

ASJC Scopus subject areas

  • Chemistry(all)

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    Benyettou, F., Prakasam, T., Ramdas Nair, A., Witzel, I. I., Alhashimi, M., Skorjanc, T., Olsen, J. C., Sadler, K. C., & Trabolsi, A. (2019). Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots. Chemical Science, 10(23), 5884-5892. https://doi.org/10.1039/c9sc01218d