DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media

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DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media. / Kostrhunova, H; Florian, J; Novakova, O; Peacock, Anna; Sadler, PJ; Brabec, V.

In: Journal of Medicinal Chemistry, Vol. 51, No. 12, 26.06.2008, p. 3635-3643.

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Kostrhunova, H ; Florian, J ; Novakova, O ; Peacock, Anna ; Sadler, PJ ; Brabec, V. / DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 12. pp. 3635-3643.

Bibtex

@article{1f2bedc5c9ca41e19a4205eed24e0221,
title = "DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media",
abstract = "This work is the first in-depth study of osmium binding to DNA and confirms the pharmacological activity of a new class of anticancer metallodrugs. We investigated the interactions between the potential biological target DNA and four osmium(II) arene complexes, of the type [(eta(6)-arene)Os(LL)Cl](n+), where arene = biphenyl or p-cymene and LL = ethylenediamine, picolinate, or oxinate in an effort to understand their mechanism of action. Most notably. we show that these complexes bind to DNA. DNA adducts of the Os-II complexes that exhibit promising cytotoxic effects in ovarian tumor cell lines largely distort its conformation. The data are consistent with DNA binding of the complexes containing biphenyl as the arene ligand that involves combined coordination to guanine residues and noncovalent interactions between the arene ligand and DNA. The results also indicate both a mechanism of action and a detoxification mechanism for Os-II arene compounds different from those of cisplatin.",
author = "H Kostrhunova and J Florian and O Novakova and Anna Peacock and PJ Sadler and V Brabec",
year = "2008",
month = jun
day = "26",
doi = "10.1021/jm701538w",
language = "English",
volume = "51",
pages = "3635--3643",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "12",

}

RIS

TY - JOUR

T1 - DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media

AU - Kostrhunova, H

AU - Florian, J

AU - Novakova, O

AU - Peacock, Anna

AU - Sadler, PJ

AU - Brabec, V

PY - 2008/6/26

Y1 - 2008/6/26

N2 - This work is the first in-depth study of osmium binding to DNA and confirms the pharmacological activity of a new class of anticancer metallodrugs. We investigated the interactions between the potential biological target DNA and four osmium(II) arene complexes, of the type [(eta(6)-arene)Os(LL)Cl](n+), where arene = biphenyl or p-cymene and LL = ethylenediamine, picolinate, or oxinate in an effort to understand their mechanism of action. Most notably. we show that these complexes bind to DNA. DNA adducts of the Os-II complexes that exhibit promising cytotoxic effects in ovarian tumor cell lines largely distort its conformation. The data are consistent with DNA binding of the complexes containing biphenyl as the arene ligand that involves combined coordination to guanine residues and noncovalent interactions between the arene ligand and DNA. The results also indicate both a mechanism of action and a detoxification mechanism for Os-II arene compounds different from those of cisplatin.

AB - This work is the first in-depth study of osmium binding to DNA and confirms the pharmacological activity of a new class of anticancer metallodrugs. We investigated the interactions between the potential biological target DNA and four osmium(II) arene complexes, of the type [(eta(6)-arene)Os(LL)Cl](n+), where arene = biphenyl or p-cymene and LL = ethylenediamine, picolinate, or oxinate in an effort to understand their mechanism of action. Most notably. we show that these complexes bind to DNA. DNA adducts of the Os-II complexes that exhibit promising cytotoxic effects in ovarian tumor cell lines largely distort its conformation. The data are consistent with DNA binding of the complexes containing biphenyl as the arene ligand that involves combined coordination to guanine residues and noncovalent interactions between the arene ligand and DNA. The results also indicate both a mechanism of action and a detoxification mechanism for Os-II arene compounds different from those of cisplatin.

U2 - 10.1021/jm701538w

DO - 10.1021/jm701538w

M3 - Article

C2 - 18494458

VL - 51

SP - 3635

EP - 3643

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 12

ER -