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

Zhidong Ma, Lu Rao, Ulrich Bierbach

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3424-3427
Number of pages4
JournalJournal of Medicinal Chemistry
Volume52
Issue number10
DOIs
StatePublished - May 28 2009
Externally publishedYes

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Amidines
Acridines
Thiourea
Acetylcysteine
Biological Factors
Platinum
Sulfur
Cysteine
Chlorides
Nitrogen
Metals
DNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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; Rao, Lu; Bierbach, Ulrich.

In: Journal of Medicinal Chemistry, Vol. 52, No. 10, 28.05.2009, p. 3424-3427.

Research output: Contribution to journalArticle

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