A Novel Design of Combining ACE Inhibitor Captopril with Angiotensin Receptor blocker Losartan Using Homo Coupling Via PEG Diacid Linker (original) (raw)

2014

Abstract

ABSTRACT Cardiovascular disease is the leading cause of deaths in American adults. Furthermore, incidents of congestive heart failure are on the rise as a major cause of hospitalization and mortality in the population. Angiotensin converting enzyme (ACE) inhibitors prevent the production of angiotensin II, and it has been shown to reduce mortality in patients with congestive heart failure. Angiotensin II receptor blockers (ARB) were developed as a direct inhibitor of angiotensin II. Unlike ACE inhibitors, ARBs have been shown to be effective in the treatment of patients with systolic heart failure without causing common side effects, such as coughing. In theory, a drug, which has both modes of actions of two drug in a single molecule, may have additive effect in the treatment of heart failure. Therefore, the purpose of this manuscript is to suggest and discuss a new molecule generated by combining captopril, an ACE inhibitor, with losartan, an ARB. In this experiment, Captopril and Losartan were modified and synthesized separately and combined by homo or mono coupling. It was achieved by taking advantage of PEG as a linker. It is expected that this molecule will have a potential of combined modes of action of an ACE inhibitors and ARB. According to the relevant recent patents, combination medication therapy has developed, resulting in effects of multiple doses of variety of medications. Benefits from combination therapy have increased efficacy, reduced adverse effects, convenience, compliance, and prolonged duration. Consequently, this combined molecule is expected to block the production of angiotensin II more efficiently and effectively. Although captopril and losartan work in the same system in blocking the effect of angiotensin II they have different action site and mechanism. Losartan acts on cell surface membrane as angiotensin receptor blocker while captopril works in plasma by blocking angiotensin converting enzymes.

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