Hydroxypyri(mi)dine-Based Chelators as Antidotes of Toxicity Due to Aluminum and Actinides

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Abstract:

This review is focused on recent developments on hydroxypyri(mi)dines, as aluminum and actinide chelating agents to combat the toxicity due to accumulations of these metal ions in human body resulting from excessive metal exposure. After a brief update revision of the most common processes of aluminum (Al) exposure, as well as the associated toxicities and pathologies, we will focus on the current available Al chelators and future perspective as potential antidotes of Al toxicity. Due to the similarity between Al and Fe, a major emphasis is given to the hydroxypyridinone and hydroxypyrimidinone chelators, since they are analogues of the current iron chelators in clinical use (DFP and DFO). This review includes issues such as molecular design strategies and corresponding effects on the associated physico-chemical properties, lipo-hydrophilic balance, toxicity, in vivo bioassays and current clinical applications. The hydroxypyri(mi)dine chelators are also suitable for other hard metal ions, such as the radiotoxic actinides, and so a brief review is included on the applications of these chelators in actinides scavenging.

Keywords: (DFP and DFO); Aluminum; actinides; antidotes of Al toxicity; chelating agents; chelating therapy; hydroxypyri(mi)dines; hydroxypyrimidinone; pathologies; radiotoxic actinides

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986712800609779

Affiliations: IST-UTL, Centro de Quimica Estrutural, Av. Rovisco Pais, 1049-001 Lisboa Portugal.

Publication date: June 1, 2012

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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