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Replacement of a thiourea-S with an amidine-NH donor group in a platinum-acridine antitumor compound reduces the metal's reactivity with cysteine sulfur.

ABSTRACT: The reactivity of two DNA-targeted platinum-acridine conjugates with cysteine sulfur was studied. The conjugate containing an amidine-NH donor group cis to the chloride leaving group showed considerably reduced reactivity with N-acetylcysteine compared to the prototypical derivative containing a thiourea-S linkage. The opposite scenario has been observed previously in reactions with nucleobase nitrogen. Possible consequences of the unique target-selective tuning of the substitution chemistry for the pharmacodynamic properties and biological activity of these agents are discussed.

SUBMITTER: Ma Z

PROVIDER: S-EPMC2693338 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Replacement of a thiourea-S with an amidine-NH donor group in a platinum-acridine antitumor compound reduces the metal's reactivity with cysteine sulfur.

Ma Zhidong Z Rao Lu L Bierbach Ulrich U

Journal of medicinal chemistry 20090501 10

The reactivity of two DNA-targeted platinum-acridine conjugates with cysteine sulfur was studied. The conjugate containing an amidine-NH donor group cis to the chloride leaving group showed considerably reduced reactivity with N-acetylcysteine compared to the prototypical derivative containing a thiourea-S linkage. The opposite scenario has been observed previously in reactions with nucleobase nitrogen. Possible consequences of the unique target-selective tuning of the substitution chemistry for ...[more]

PMID: 19397321

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