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, Mohammad R Movahed

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)221-225
Number of pages5
JournalRecent Patents on Cardiovascular Drug Discovery
Volume8
Issue number3
DOIs
StatePublished - 2013

Fingerprint

Losartan
Angiotensin Receptor Antagonists
Captopril
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II
Heart Failure
Systolic Heart Failure
Patents
Mortality
Proxy
Peptidyl-Dipeptidase A
Plasma Cells
Compliance
Smooth Muscle Myocytes
Cause of Death
Hospitalization
Cardiovascular Diseases
Incidence
Therapeutics
Population

Keywords

  • ACE i
  • Acute coronary syndrome
  • Angiotensin converting enzyme inhibitor
  • Angiotensin receptor blocker
  • ARB
  • Blood pressure
  • Captopril
  • Hypertension
  • Losartan
  • PEG linker

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)
  • Drug Discovery
  • Medicine(all)

Cite this

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title = "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",
abstract = "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",
author = "Mehrnoosh Hashemzadeh and Shery Park and Hee Ju and Movahed, {Mohammad R}",
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T1 - 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

AU - Hashemzadeh, Mehrnoosh

AU - Park, Shery

AU - Ju, Hee

AU - Movahed, Mohammad R

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