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

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2009 Apr 29

PMID 19397321

Citations 12

Authors

Zhidong Ma

Lu Rao

Ulrich Bierbach

Affiliations

Soon will be listed here.

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.

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