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Molecular mechanisms and proposed targets for selected anticancer gold compounds

Casini, Angela and Messori, Luigi 2011. Molecular mechanisms and proposed targets for selected anticancer gold compounds. Current Topics in Medicinal Chemistry 11 (21) , pp. 2647-2660. 10.2174/156802611798040732

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Nowadays, gold compounds constitute a family of very promising experimental agents for cancer treatment. Indeed, several gold(I) and gold(III) compounds were shown to manifest outstanding antiproliferative properties in vitro against selected human tumor cell lines and some of them performed remarkably well even in tumor models in vivo. Notably, the peculiar chemical properties of the gold centre impart innovative pharmacological profiles to gold-based metallodrugs most likely in relation to novel molecular mechanisms. The precise mechanisms through which cytotoxic gold compounds produce their biological effects are still largely unknown. Within this frame, the major aim of this review is to define the possible modes of action and the most probable biomolecular targets for a few representative gold compounds on which extensive biochemical and cellular data have been gathered. In particular, we will focus on auranofin and analogues, on gold(III) porphyrins and gold(III) dithiocarbamates. For these three families markedly distinct molecular mechanisms were recently invoked: a direct mitochondrial mechanism involving thioredoxin reductase inhibition in the case of the gold(I) complexes, the influence on some apoptotic proteins - i.e. MAPKs and Bcl-2 - for gold(III) porphyrins, and the proteasome inhibition for gold(III) dithiocarbamates. In a few cases the distinct mechanisms may overlap. The general perspectives for the development of new gold compounds as effective anticancer agents with innovative modes of action are critically discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Bentham Science Publishers
ISSN: 1568-0266
Last Modified: 04 Jun 2017 08:30

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