Oliveira, Jonas Ivan NobreEsmaile, Stephany Campanelli2019-03-082019-03-082019-02-15ESMAILE, Stephany Campanelli. Modelagem molecular do fármaco olmesartana acoplado ao receptor de angiotensina AT1 em pH ácido ou fisiológico. 2019. 47f. Dissertação (Mestrado em Ciências Biológicas) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2019.https://repositorio.ufrn.br/jspui/handle/123456789/26702Hypertension is a risk factor for stroke, which predisposes patients to motor and cognitive impairments. 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 6.2 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 6.2 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. The results indicate the main amino acids of the AT1 receptor interacting with OLM, as well as the 105 amino acids present in a 10Å radius that add -588.25kcal/mol at pH 6.2 and -411.12 kcal/mol at pH 7.3. This implies that the interaction energy of the AT1 receptor with OLM at pH6.2 is higher than at pH 7.3. The hypothesis is that the neuroregenerative effects of OLM will be longer at pathological pH, which may be enhanced by the increased availability of angiotensin II to the AT2 receptor. Our data are in agreement with those in the literature that elucidate the therapeutic potential of this drug in post-stroke brains.Acesso AbertoReceptor de AngiotensinaOlmesartanapHMFCCDFTmasterThesisCNPQ::CIENCIAS BIOLOGICAS