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New Copper Compounds with Antiplatelet Aggregation Activity

Author(s):

Mirthala Flores-Garcia, Juan Manuel Fernández-G, Cristina Busqueta-Griera, Elizabeth Gomez, Simon Hernandez-Ortega, Jean Christian Daniel Lamothe-Flores, Virginia Gomez-Vidales, Ana Maria Mejia-Dominguez, Eduardo Angles-Cano and Aurora de la Pena-Diaz*  

Abstract:


Background: Ischemic heart disease, cerebrovascular accident, and venous thromboembolism have the presence of a thrombotic event in common and represent the most common causes of death within the population.

Objective: Since Schiff base copper(II) complexes are able to interact with polyphosphates (PolyP), a procoagulant and potentially prothrombotic platelet agent, we investigated the antiplatelet aggregating properties of two novel tridentate Schiff base ligands and their corresponding copper(II) complexes.

Methods: The Schiff base ligands (L1) and (L2), as well as their corresponding copper(II) complexes (C1) and (C2), were synthesized and characterized by chemical analysis, X-ray diffraction, mass spectrometry, and UV-Visible, IR and far IR spectroscopy. In addition, EPR studies were carried out for (C1) and (C2), while (L1) and (L2) were further analyzed by 1H and 13C NMR. Tests for antiplatelet aggregation activities of all of the four compounds were conducted.

Results: X-ray diffraction studies show that (L1) and (L2) exist in the enol-imine tautomeric form with a strong intramolecular hydrogen bond. NMR studies show that both ligands are found as enol-imine tautomers in CDCl3 solution. In the solid state, the geometry around the copper(II) ion in both (C1) and (C2) is square planar. EPR spectra suggest that the geometry of the complexes is similar to that observed in the solid state by X-ray crystallography. Compound (C2) exhibited the strongest antiplatelet aggregation activity.

Conclusion: Schiff base copper(II) complexes, which are attracting increasing interest, could represent a new approach to treat thrombosis by blocking the activity of PolyP with a potential anticoagulant activity and, most importantly, demonstrating no adverse bleeding events.

Keywords:

Copper(II) complexes, antiplatelet activity, polyphosphates

Affiliation:

Instituto Nacional de Cardiología Ignacio Chavez. Juan Badiano 1, Tlalpan 14080, Ciudad de Mexico, Instituto de Quimica. Universidad Nacional Autonoma de Mexico. Circuito Exterior, Ciudad. Universitaria, Coyoacan 04510, Ciudad de Mexico, Instituto de Quimica. Universidad Nacional Autonoma de Mexico. Circuito Exterior, Ciudad. Universitaria, Coyoacan 04510, Ciudad de Mexico, Instituto de Quimica. Universidad Nacional Autonoma de Mexico. Circuito Exterior, Ciudad. Universitaria, Coyoacan 04510, Ciudad de Mexico, Instituto de Quimica. Universidad Nacional Autonoma de Mexico. Circuito Exterior, Ciudad. Universitaria, Coyoacan 04510, Ciudad de Mexico, Instituto Nacional de Cardiología Ignacio Chavez. Juan Badiano 1, Tlalpan 14080, Ciudad de Mexico, Instituto de Quimica. Universidad Nacional Autonoma de Mexico. Circuito Exterior, Ciudad. Universitaria, Coyoacan 04510, Ciudad de Mexico, Instituto Nacional de Cardiología Ignacio Chavez. Juan Badiano 1, Tlalpan 14080, Ciudad de Mexico, INSERM UMR-S1140. Fac. Sciences Pharmaceutiques & Biologiques. Avenue de l`Observatoire. 75270 Paris, Cedex 06, Instituto Nacional de Cardiología Ignacio Chavez. Juan Badiano 1, Tlalpan 14080, Ciudad de Mexico



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