A Novel Design of Combining the Angiotensin Converting Enzyme (ACE) Inhibitor Captopril with the Angiotensin Receptor Blocker (ARB) Losartan Using Homo Coupling via PEG Diacid Linker
Mehrnoosh Hashemzadeh, Shery Park, Hee Ju and Mohammad R. Movahed
Affiliation: University of Arizona Sarver Heart Center, 6119 North Pinchot, Tucson, AZ,USA 85750.
Cardiovascular disease is the leading cause of death in American adults. Furthermore, the incidence of congestive
heart failure is on the rise as a major cause of hospitalization and mortality in this population. Angiotensin Converting
Enzyme (ACE) inhibitors prevent the production of angiotensin II, which 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. ARBs have been shown to
be effective in the treatment of patients with systolic heart failure but do not cause chronic coughing which is a common
side effect of ACE inhibitors. In theory, a compound that has the combined effect of an ACE inhibitor and an ARB should
be more effective in treating heart failure patients than either agents alone. Therefore, the purpose of this manuscript is to
design and discuss the benefits of a new molecule, which combines 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.
This was achieved by taking advantage of PEG (Polyethylene glycol) as a linker. It is expected that this molecule
will have the combined modes of action of both ACEs and ARBs. Benefits from combination therapy include; 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 by blocking the effect of angiotensin II they have different action sites and mechanisms some
patents are also discussed. Losartan blocks the AT1 receptor which is expressed on the cell surface, while captopril inhibits
ACE, preventing production of angiotensin II, which is present in both the plasma and on the cell surface, especially on
endothelial and smooth muscle cells.
Keywords: ACE I, acute coronary syndrome, angiotensin converting enzyme inhibitor, angiotensin receptor blocker, ARB,
blood pressure, Captopril, hypertension, Losartan, PEG linker.
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