Losartan as an ACE inhibitor: a description of the mechanism of action through quantum biochemistry.
Eveline M BezerraÉrika L F C de AlvarengaRicardo P Dos SantosJeanlex S de SousaUmberto Laino FulcoValder N FreireEudenilson L AlbuquerqueRoner F da CostaPublished in: RSC advances (2022)
Losartan (LST) is a potent and selective angiotensin II (Ang II) type 1 (AT1) receptor antagonist widely used in the treatment of hypertension. The formation of Ang II is catalyzed by the angiotensin I-converting enzyme (ACE) through proteolytic cleavage of angiotensin I (Ang I), which is involved in the control of blood pressure. Despite the vast literature on the relationship of losartan with the renin-angiotensin system (RAS), the actions of losartan on the sACE enzyme are so far poorly understood. In view of this, we investigated how losartan can interact with the sACE enzyme to block its activity and intracellular signaling. After performing docking assays following quantum biochemistry calculations using losartan and sACE crystallographic data, we report that their interaction results reveal a new mechanism of action with important implications for understanding its effects on hypertension.
Keyphrases
- angiotensin ii
- angiotensin converting enzyme
- blood pressure
- molecular dynamics
- vascular smooth muscle cells
- molecular dynamics simulations
- systematic review
- hypertensive patients
- heart rate
- density functional theory
- gene expression
- dna methylation
- mass spectrometry
- adipose tissue
- electronic health record
- big data
- single cell
- protein protein
- weight loss
- artificial intelligence
- room temperature
- smoking cessation
- single molecule
- anti inflammatory