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Design, synthesis and pharmacological evaluation of new resveratrol derivatives useful for dyslipidemia treatment

Grant number: 14/03945-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2014
Effective date (End): December 31, 2017
Field of knowledge:Health Sciences - Pharmacy - Medicines Analysis and Control
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Jean Leandro dos Santos
Grantee:Luiz Antonio Dutra
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):15/21271-8 - Pharmacological evaluation of resveratrol derivatives as dual bromodomain/PPARs inhibitors to treat dyslipidemia, BE.EP.DR


In Brazil, cardiovascular diseases contribute to the increased rate of mortality in allregions, representing 30% of all deaths in the country in individuals between 30 and 69 years. Contribute to the risk factors of cardiovascular disease, dyslipidemia. Dyslipidemia is characterized by changes in serum lipids and may be classified into isolated hypercholesterolemia (high LDL), hypertriglyceridemia (high levels of triglycerides), mixed hyperlipidemia (high LDL and triglycerides), low HDL. These changes contribute to the development of atherosclerosis, characterized by accumulation of lipids in arteries and vessels leading to the formation of atheroma. The latter block or decrease the size of the vessels causing isquêmicos. A therapy for the treatment of dyslipidemia events is accomplished by drugs which reduce serum LDL, such as the statins. This class of drug has low efficacy in raising HDL, a factor that is directly associated with increased risk of developing ischemic heart disease. Many of the patients who use this therapy are still subject to cardiovascular events due to the low plasma HDL. Therapeutic alternatives are used alone or combined with statins for greater effectiveness in the treatment of dyslipidemia, such as fibrates, drugs that promote increased HDL and reduced triglycerides to activate PPAR - ± receptor. However, this class of compounds has limitations in response to treatment side effects when used in combination with statins or not. Resveratrol is a natural compound classified as a polyphenol, and several cardioprotective effects of this compound are described, for example the increase in plasma HDL, LDL and triglyceride reduction. Such properties are related to the antagonism of PPAR- ±. Resveratrol is considered a model for obtaining new prototypes in the development of new drugs dyslipidemia. Molecular hybridization is a strategy for drug discovery which is the union of two different subunits of compounds of known biological activity, for obtaining a new chemical structure with double or synergistic activity. Because current therapy for the treatment of dyslipidemia has limitations, the approach of molecular hybridization is a useful strategy for the discovery of new drugs dyslipidemia. Using molecular hybridization between fibrates and resveratrol we have intended to seek novel, secure and potential compounds for dyslipidemia treatment. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DUTRA, LUIZ ANTONIO; GUANAES, JESSICA FRADE O.; JOHMANN, NADINE; LOPES PIRES, MARIA ELISA; CHIN, CHUNG MAN; MARCONDES, SISI; DOS SANTOS, JEAN LEANDRO. Synthesis, antiplatelet and antithrombotic activities of resveratrol derivatives with NO-donor properties. Bioorganic & Medicinal Chemistry Letters, v. 27, n. 11, p. 2450-2453, . (15/19531-1, 11/15520-4, 15/21271-8, 14/03945-9)
DUTRA, LUIZ ANTONIO; HEIDENREICH, DAVID; BERNARDES DA SILVA, GABRIEL DALIO; CHIN, CHUNG MAN; KNAPP, STEFAN; DOS SANTOS, JEAN LEANDRO. Dietary Compound Resveratrol Is a Pan-BET Bromodomain Inhibitor. NUTRIENTS, v. 9, n. 11, . (16/08880-8, 15/19531-1, 14/03945-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
DUTRA, Luiz Antonio. Planejamento, síntese e avaliação farmacológica de novos compostos híbridos derivados de resveratrol e bezafibrato úteis ao tratamento da dislipidemia. 2017. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.

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