Development of Zeise's Salt Derivatives Bearing Substituted Acetylsalicylic Acid Substructures as Cytotoxic COX Inhibitors.

Zeise's salt derivatives of the potassium trichlorido[η-((prop-2-en/but-3-en)-1-yl)-2-acetoxybenzoate]platinate(II) type (ASA-Prop-PtCl/ASA-But-PtCl derivatives) were synthesized and characterized regarding their structure, stability, and biological activity. It is proposed that the leads ASA-Prop-PtCl and ASA-But-PtCl interfere with the arachidonic acid cascade as part of their mode of action to reduce the growth of COX-1/2-expressing tumor cells. With the aim to increase the antiproliferative activity by strengthening the inhibitory potency against COX-2, F, Cl, or CH substituents were introduced into the acetylsalicylic acid (ASA) moiety.

Synthesis and Biological Evaluation of Zeise's Salt Derivatives with Acetylsalicylic Acid Substructure.

The development of novel biologically active organometallic compounds bearing an acetylsalicylic acid (ASA) substructure led to the synthesis of analogical Zeise-type salts that accordingly inhibit cyclooxygenase (COX) enzymes. In order to determine the influence of the length of the alkyl chain between the platinum(II) center and the ASA moiety, compounds with varying methylene groups ( = 1⁻4) were synthesized and characterized. For the propene derivative structural elucidation by X-ray crystallography was possible.