Nitrosyl active sites of ferredoxines biomimetics as NO donors for acute coronary syndrome therapy

Abstract

In studies of the reaction mechanisms of NO intermediates, the synthesis of analogs of cellular nitrosyl adducts has gained increasing importance. It has been reliably established that iron nitrosyl complexes with thiol-containing ligands play important roles in organisms, such as cellular NO storage and transport. Synthesis of synthetic analogs modeling nitrosyl [2Fe-2S] proteins reactivity is an important problem from the point of view practical medicine for the design prodrugs based on natural sources. Recent research in the field of molecular cardiology revealed the key role of NO in the regulation of vascular tone and metabolism of myocardium. The lack of NO results in the development of endothelial disfunction, which in turn is a reason of higher tone of coronary vessels and higher aggregation and adhesion capability of thrombocytes. Ischemic and reperfusion disruption provide the development of the “no reflow” syndrome, which results in the progressive deterioration of blood flow and finally the death of cardiac hystiocytes. Nitrosyl iron complexes with functional sulfur-containing ligands were studied on the models of ischemic and reperfusion heart damage of rats Wistar in vitro and in vivo, and were shown to have a cardioprotective effect. They can be used for the preparation of unique medications in the therapy of acute coronary event. Vasodilatation properties of these compounds affect the restoration of coronary flow; reduction of systolic blood pressure; improvement of restoration, metabolism and heart function after ischemia; reduction of the dimensions of myocardial infarction.