Antitumor and DNA-Binding Properties of a Group of Oligomeric Complexes of Pt(II) and Pt(IV)

Adam Peritz; Salaam Al-Baker; Jean F. Vollano; James C. Dabrowiak; John E. Schurig; William T. Bradner

doi:10.1021/jm00170a022

Antitumor and DNA-Binding Properties of a Group of Oligomeric Complexes of Pt(II) and Pt(IV)

Adam Peritz, Salaam Al-Baker, Jean F. Vollano, James C. Dabrowiak, John E. Schurig, William T. Bradner

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

The antitumor and DNA-binding properties of a group of oligomeric platinum(II) and platinum(IV) complexes are described. The compounds, having the stoichiometry [cis-Pt^II(X)₂(µ-0H)]₂(N0₃)₂, where X is NH₃, NH₂CH₂CH₃, and NH₂CH(CH₃)₂, were found to be inactive or only weakly active against L-1210 leukemia. In vitro studies involving PM2-DNA show that these compounds bind to and unwind closed circular DNA in a manner similar to cis-Pt¹¹-(NH₃)₂C1₂. The Pt(IV) complexes produced by hydrogen peroxide oxidation of the Pt(II) dimers are inactive as antitumor agents and are incapable of unwinding PM2-DNA. The cyclotrimer [cis-Pt^II(RR-DACH)(µ-0H)]₃(N0₃)₃, where RR-DACH is (R,R)-1,2 diaminocyclohexane, exhibits potent antitumor activity against L-1210 leukemia and modest activities with B-16 and M5076 tumor lines. This compound platinates DNA, causing DNA unwinding and mobility shifts.

Original language	English (US)
Pages (from-to)	2184-2188
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	33
Issue number	8
DOIs	https://doi.org/10.1021/jm00170a022
State	Published - 1990

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Antitumor and DNA-Binding Properties of a Group of Oligomeric Complexes of Pt(II) and Pt(IV)",

abstract = "The antitumor and DNA-binding properties of a group of oligomeric platinum(II) and platinum(IV) complexes are described. The compounds, having the stoichiometry [cis-PtII(X)2(µ-0H)]2(N03)2, where X is NH3, NH2CH2CH3, and NH2CH(CH3)2, were found to be inactive or only weakly active against L-1210 leukemia. In vitro studies involving PM2-DNA show that these compounds bind to and unwind closed circular DNA in a manner similar to cis-Pt11-(NH3)2C12. The Pt(IV) complexes produced by hydrogen peroxide oxidation of the Pt(II) dimers are inactive as antitumor agents and are incapable of unwinding PM2-DNA. The cyclotrimer [cis-PtII(RR-DACH)(µ-0H)]3(N03)3, where RR-DACH is (R,R)-1,2 diaminocyclohexane, exhibits potent antitumor activity against L-1210 leukemia and modest activities with B-16 and M5076 tumor lines. This compound platinates DNA, causing DNA unwinding and mobility shifts.",

author = "Adam Peritz and Salaam Al-Baker and Vollano, {Jean F.} and Dabrowiak, {James C.} and Schurig, {John E.} and Bradner, {William T.}",

year = "1990",

doi = "10.1021/jm00170a022",

language = "English (US)",

volume = "33",

pages = "2184--2188",

journal = "Journal of Medicinal Chemistry",

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T1 - Antitumor and DNA-Binding Properties of a Group of Oligomeric Complexes of Pt(II) and Pt(IV)

AU - Peritz, Adam

AU - Al-Baker, Salaam

AU - Vollano, Jean F.

AU - Dabrowiak, James C.

AU - Schurig, John E.

AU - Bradner, William T.

PY - 1990

Y1 - 1990

N2 - The antitumor and DNA-binding properties of a group of oligomeric platinum(II) and platinum(IV) complexes are described. The compounds, having the stoichiometry [cis-PtII(X)2(µ-0H)]2(N03)2, where X is NH3, NH2CH2CH3, and NH2CH(CH3)2, were found to be inactive or only weakly active against L-1210 leukemia. In vitro studies involving PM2-DNA show that these compounds bind to and unwind closed circular DNA in a manner similar to cis-Pt11-(NH3)2C12. The Pt(IV) complexes produced by hydrogen peroxide oxidation of the Pt(II) dimers are inactive as antitumor agents and are incapable of unwinding PM2-DNA. The cyclotrimer [cis-PtII(RR-DACH)(µ-0H)]3(N03)3, where RR-DACH is (R,R)-1,2 diaminocyclohexane, exhibits potent antitumor activity against L-1210 leukemia and modest activities with B-16 and M5076 tumor lines. This compound platinates DNA, causing DNA unwinding and mobility shifts.

AB - The antitumor and DNA-binding properties of a group of oligomeric platinum(II) and platinum(IV) complexes are described. The compounds, having the stoichiometry [cis-PtII(X)2(µ-0H)]2(N03)2, where X is NH3, NH2CH2CH3, and NH2CH(CH3)2, were found to be inactive or only weakly active against L-1210 leukemia. In vitro studies involving PM2-DNA show that these compounds bind to and unwind closed circular DNA in a manner similar to cis-Pt11-(NH3)2C12. The Pt(IV) complexes produced by hydrogen peroxide oxidation of the Pt(II) dimers are inactive as antitumor agents and are incapable of unwinding PM2-DNA. The cyclotrimer [cis-PtII(RR-DACH)(µ-0H)]3(N03)3, where RR-DACH is (R,R)-1,2 diaminocyclohexane, exhibits potent antitumor activity against L-1210 leukemia and modest activities with B-16 and M5076 tumor lines. This compound platinates DNA, causing DNA unwinding and mobility shifts.

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JO - Journal of Medicinal Chemistry

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Antitumor and DNA-Binding Properties of a Group of Oligomeric Complexes of Pt(II) and Pt(IV)

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