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The Biological Activity of Zeise’s Salt and its Derivatives
Author(s) -
Meieranz Sandra,
Stefanopoulou Maria,
Rubner Gerhard,
Bensdorf Kerstin,
Kubutat Dominic,
Sheldrick William S.,
Gust Ronald
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201410357
Subject(s) - chemistry , enzyme , stereochemistry , biochemistry
With the aim to design new biologically active bioinorganic drugs of aspirin, whose mode of action is based on the inhibition of the cyclooxygenase(COX) enzymes, derivatives of Zeise’s salt were synthesized in this structure–activity relationship study. Surprisingly, not only these Zeise–aspirin compounds but also Zeise’s salt itself showed high inhibitory potency against COX enzymes in in vitro assays. In contrast, potassium tetrachloroplatinate and cisplatin did not influence the enzyme activity at equimolar concentrations. It was demonstrated by LC‐ESI tandem‐mass spectrometry that Zeise’s salt platinates the essential amino acids Tyr385 (active site of the enzyme) and Ser516 (will be acetylated by aspirin) of COX‐1, thereby strongly impairing the function of the enzyme. This finding demonstrates for the first time that Zeise’s salt is pharmacologically active and is a potent enzyme inhibitor.