Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors

The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synt...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2015-03, Vol.20 (3), p.3868-3897
Main Authors: Kellici, Tahsin F, Tzakos, Andreas G, Mavromoustakos, Thomas
Format: Article
Language:English
Subjects:
Angiotensin II - metabolism
angiotensin II receptors
Angiotensin II Type 1 Receptor Blockers - pharmacology
Angiotensin II Type 1 Receptor Blockers - therapeutic use
Animals
AT1R
AT2R
Cardiovascular Diseases - metabolism
Drug Design
drug-membrane interactions
Humans
molecular modeling
Quantitative Structure-Activity Relationship
rational drug design
Receptor, Angiotensin, Type 1 - metabolism
Receptor, Angiotensin, Type 2 - metabolism
Review
synthesis
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Summary:The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synthesize compounds that affect beneficially these two receptors. Cardiovascular disease, which is attributed to the overactivation of the vasoactive peptide hormone Αng II, can now be treated with commercial AT1R antagonists. Herein, recent achievements in rational drug design and synthesis of molecules acting on the two AT receptors are reviewed. Quantitative structure activity relationships (QSAR) and molecular modeling on the two receptors aim to assist the search for new active compounds. As AT1R and AT2R are GPCRs and drug action is localized in the transmembrane region the role of membrane bilayers is exploited. The future perspectives in this field are outlined. Tremendous progress in the field is expected if the two receptors are crystallized, as this will assist the structure based screening of the chemical space and lead to new potent therapeutic agents in cardiovascular and other diseases.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules20033868