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

doi:10.1039/c9sc01218d

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	5884-5892
Number of pages	9
Journal	Chemical Science
Volume	10
Issue number	23
DOIs	https://doi.org/10.1039/c9sc01218d
State	Published - Jun 21 2019

ASJC Scopus subject areas

General Chemistry

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10.1039/c9sc01218d

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title = "Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots",

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.",

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

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doi = "10.1039/c9sc01218d",

language = "English (US)",

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T1 - Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots

AU - Benyettou, Farah

AU - Prakasam, Thirumurugan

AU - Ramdas Nair, Anjana

AU - Witzel, Ini Isabee

AU - Alhashimi, Marwa

AU - Skorjanc, Tina

AU - Olsen, John Carl

AU - Sadler, Kirsten C.

AU - Trabolsi, Ali

PY - 2019/6/21

Y1 - 2019/6/21

N2 - 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.

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

Abstract

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