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 Sadler Edepli, 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 - Jan 1 2019

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Metals
Cells
Cisplatin
Synthetic metals
Cell membranes
Cytotoxicity
Chelation
Self assembly
Reactive Oxygen Species
Apoptosis
Ligands
DNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Benyettou, F., Prakasam, T., Ramdas Nair, A., Witzel, I. I., Alhashimi, M., Skorjanc, T., ... 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

Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots. / Benyettou, Farah; Prakasam, Thirumurugan; Ramdas Nair, Anjana; Witzel, Ini Isabee; Alhashimi, Marwa; Skorjanc, Tina; Olsen, John Carl; Sadler Edepli, Kirsten; Trabolsi, Ali.

In: Chemical Science, Vol. 10, No. 23, 01.01.2019, p. 5884-5892.

Research output: Contribution to journalArticle

Benyettou, F, Prakasam, T, Ramdas Nair, A, Witzel, II, Alhashimi, M, Skorjanc, T, Olsen, JC, Sadler Edepli, K & Trabolsi, A 2019, 'Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots', Chemical Science, vol. 10, no. 23, pp. 5884-5892. https://doi.org/10.1039/c9sc01218d
Benyettou F, Prakasam T, Ramdas Nair A, Witzel II, Alhashimi M, Skorjanc T et al. Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots. Chemical Science. 2019 Jan 1;10(23):5884-5892. https://doi.org/10.1039/c9sc01218d
Benyettou, Farah ; Prakasam, Thirumurugan ; Ramdas Nair, Anjana ; Witzel, Ini Isabee ; Alhashimi, Marwa ; Skorjanc, Tina ; Olsen, John Carl ; Sadler Edepli, Kirsten ; Trabolsi, Ali. / Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots. In: Chemical Science. 2019 ; Vol. 10, No. 23. pp. 5884-5892.
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