Development of a New Class of Pharmacological Mediators for Myeloperoxidase Inhib

Rajagopal, Desikan

Abstract

Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels especially those related to atherosclerosis (arterial disease). This disease is the number one killer around the world, particularly in the United States. Myeloperoxidase (MPO) enzyme has been implicated in many cardiovascular diseases and to date there is no single drug available for treatment. The development of new drug candidates against myeloperoxidase (MPO) may prove to be useful in the prevention of the progression of vulnerable atherosclerotic plaque. We propose the development of a new class of pharmacological mediators for myeloperoxidase inhibition based on naturally available chemical structures. Our preliminary studies identified two specific MPO inhibitors by evaluating their efficacy using in vitro model. The salient features of the proposed inhibitors are that these inhibitors are specific toward MPO as well as their generic anti oxidant properties. The feasibility study has specific aims as listed below:

Public Health Relevance

Atherosclerosis is a leading cause of coronary heart disease and stroke, which are responsible for more than 25% of all deaths in the United States and more than 8 millions Americans are affected by peripheral heart disease. Myeloperoxidase enzyme has been reported to have leading cause for cardiovascular disease including atherosclerosis. To date there is no single drug available for the treatment against myeloperoxidase enzyme. Therefore, there is an urgent need to identify new therapies against myeloperoxidase enzyme. The objective of the proposed study is to identify a new class of pharmacological mediators for MPO inhibition and study their efficacies both in vitro and in vivo model.