Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design

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Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design. / Romero-Canelón, Isolda; Soldevila-Barreda, Joan J.; Habtemariam, Abraha; Sadler, Peter J.

In: Nature Communications, Vol. 6, 6582, 20.03.2015.

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Romero-Canelón, Isolda ; Soldevila-Barreda, Joan J. ; Habtemariam, Abraha ; Sadler, Peter J. / Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design. In: Nature Communications. 2015 ; Vol. 6.

Bibtex

@article{596d5dcf46024a429a2a80e10c9003b8,
title = "Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design",
abstract = "Organometallic complexes are effective hydrogenation catalysts for organic reactions. For example, Noyori-type ruthenium complexes catalyse reduction of ketones by transfer of hydride from formate. Here we show that such catalytic reactions can be achieved in cancer cells, offering a new strategy for the design of safe metal-based anticancer drugs. The activity of ruthenium(II) sulfonamido ethyleneamine complexes towards human ovarian cancer cells is enhanced by up to 50 × in the presence of low non-toxic doses of formate. The extent of conversion of coenzyme NAD + to NADH in cells is dependent on formate concentration. This novel reductive stress mechanism of cell death does not involve apoptosis or perturbation of mitochondrial membrane potentials. In contrast, iridium cyclopentadienyl catalysts cause cancer cell death by oxidative stress. Organometallic complexes therefore have an extraordinary ability to modulate the redox status of cancer cells.",
author = "Isolda Romero-Canel{\'o}n and Soldevila-Barreda, {Joan J.} and Abraha Habtemariam and Sadler, {Peter J.}",
year = "2015",
month = mar,
day = "20",
doi = "10.1038/ncomms7582",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design

AU - Romero-Canelón, Isolda

AU - Soldevila-Barreda, Joan J.

AU - Habtemariam, Abraha

AU - Sadler, Peter J.

PY - 2015/3/20

Y1 - 2015/3/20

N2 - Organometallic complexes are effective hydrogenation catalysts for organic reactions. For example, Noyori-type ruthenium complexes catalyse reduction of ketones by transfer of hydride from formate. Here we show that such catalytic reactions can be achieved in cancer cells, offering a new strategy for the design of safe metal-based anticancer drugs. The activity of ruthenium(II) sulfonamido ethyleneamine complexes towards human ovarian cancer cells is enhanced by up to 50 × in the presence of low non-toxic doses of formate. The extent of conversion of coenzyme NAD + to NADH in cells is dependent on formate concentration. This novel reductive stress mechanism of cell death does not involve apoptosis or perturbation of mitochondrial membrane potentials. In contrast, iridium cyclopentadienyl catalysts cause cancer cell death by oxidative stress. Organometallic complexes therefore have an extraordinary ability to modulate the redox status of cancer cells.

AB - Organometallic complexes are effective hydrogenation catalysts for organic reactions. For example, Noyori-type ruthenium complexes catalyse reduction of ketones by transfer of hydride from formate. Here we show that such catalytic reactions can be achieved in cancer cells, offering a new strategy for the design of safe metal-based anticancer drugs. The activity of ruthenium(II) sulfonamido ethyleneamine complexes towards human ovarian cancer cells is enhanced by up to 50 × in the presence of low non-toxic doses of formate. The extent of conversion of coenzyme NAD + to NADH in cells is dependent on formate concentration. This novel reductive stress mechanism of cell death does not involve apoptosis or perturbation of mitochondrial membrane potentials. In contrast, iridium cyclopentadienyl catalysts cause cancer cell death by oxidative stress. Organometallic complexes therefore have an extraordinary ability to modulate the redox status of cancer cells.

UR - http://www.scopus.com/inward/record.url?scp=84924313275&partnerID=8YFLogxK

U2 - 10.1038/ncomms7582

DO - 10.1038/ncomms7582

M3 - Article

C2 - 25791197

AN - SCOPUS:84924313275

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 6582

ER -