Cisplatin Analogs Confer Protection against Cyanide Poisoning.

Cell Chem Biol
Authors
Keywords
Abstract

Cisplatin holds an illustrious position in the history of chemistry most notably for its role in the virtual cure of testicular cancer. Here we describe a role for this small molecule in cyanide detoxification in vivo. Cyanide kills organisms as diverse as insects, fish, and humans within seconds to hours. Current antidotes exhibit limited efficacy and are not amenable to mass distribution requiring the development of new classes of antidotes. The binding affinity of the cyanide anion for the positively charged metal platinum is known to create an extremely stable complex in vitro. We therefore screened a panel of diverse cisplatin analogs and identified compounds that conferred protection from cyanide poisoning in zebrafish, mice, and rabbits. Cumulatively, this discovery pipeline begins to establish the characteristics of platinum ligands that influence their solubility, toxicity, and efficacy, and provides proof of concept that platinum-based complexes are effective antidotes for cyanide poisoning.

Year of Publication
2017
Journal
Cell Chem Biol
Volume
24
Issue
5
Pages
565-575.e4
Date Published
2017 May 18
ISSN
2451-9448
DOI
10.1016/j.chembiol.2017.03.013
PubMed ID
28416275
PubMed Central ID
PMC5472353
Links
Grant list
U54 NS079201 / NS / NINDS NIH HHS / United States