Banca de QUALIFICAÇÃO: STEPHANY CAMPANELLI ESMAILE

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : STEPHANY CAMPANELLI ESMAILE
DATA : 01/02/2019
HORA: 14:00
LOCAL: Sala II - DBF
TÍTULO:

Molecular Modeling of Olmesartan Bound to Angiotensin AT1 Receptor at Acid and Physiological pH

PALAVRAS-CHAVES:

Angiotensin Receptor. Olmesartan. pH. MFCC. DFT.

PÁGINAS: 52
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biofísica
RESUMO:

Hypertension is a risk factor for stroke, which predisposes patients to cognitive impairment and dementia. Excessive AT1 receptor activity in the brain is associated with exaggerated sympathetic and hormonal responses caused by stress, vulnerability to cerebrovascular ischemia and cerebral inflammation, processes leading to neuronal injury. Therefore, the use of antihypertensives such as Olmesartan medoxomil (Benicar ®) is shown to be promising in the prevention and treatment of both ischemic and hemorrhagic stroke. Olmesartan belongs to the family of angiotensin receptor blockers (ARBs) and acts as an inverse agonist. It has high selectivity and potency for the AT1 receptor, is well tolerated, with side effect profile similar to placebo and has been shown to be more effective in the treatment of hypertension than other ARBs. Cerebral endothelial cells and astrocytes, constituents of the blood-brain barrier, are rich in AT1 receptor in their membranes and the degree of drug-receptor affinity depends on the pH of the medium. Brain regions affected by inflammation or ischemia may reach a pH of up to 6.1 in the extracellular medium, with normal pH being 7.3. The present work aims at comparing the nature and proportion of intermolecular interactions of the olmesartan-AT1 receptor crystal at pH 6.1 and 7.3, as well as quantifying the binding energies between the amino acids of the receptor and the drug up to a radius of 10Å.

MEMBROS DA BANCA:
Presidente - 2985070 - JONAS IVAN NOBRE OLIVEIRA
Interno - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Interno - 1379465 - GILBERTO CORSO