Design and synthesis of new anti-inflammatory steroids of Lapdesf FT-GL and GL-TAU series with potential anti-VEGF activity

• Grant number: 14/08728-6
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2014
• Effective date (End): February 28, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Chung Man Chin
• Grantee: Marcella Gabrielle Mendes Machado
• Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Glucocorticoids (GCs), steroidal anti-inflammatory drugs, are widely used in therapy mainly for their anti-inflammatory, immunosuppressive and antiangiogenic activities. They have the ability to reduce the transcription of several enzymes / inflammatory proteins such as cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS); proinflammatory cytokines and vascular endothelial growth factor (VEGF). The modulation of the cytokine tumor necrosis factor alpha (TNF-±), over expressed in many inflammatory diseases has become an interesting approach in the treatment of chronic inflammatory diseases, especially those patients who do not respond to conventional treatment. Thus, in the present study, have been planned by molecular hybridization strategy, new steroidal anti-inflammatory derivatives as modulators of TNF-± cytokine with potential anti-VEGF activity, useful in the treatment of chronic inflammatory diseases, including ocular diseases. In this context, will be synthesized and characterized prednisolone and budesonide derivatives of Lapdesf GL-FT and Lapdesf GL-TAU series. The compounds will be evaluated for anti-inflammatory activity in distal ulcerative colitis, production of proinflammatory cytokines, experimental determination of log P and VEGF expression. It is expected that the proposed derivatives exhibit anti-inflammatory and anti-VEGF activity superior to the standard (prednisolone and budesonide). (AU)

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)

MENDES MACHADO, MARCELLA GABRIELLE; SCARIM, CAUE BENITO; DE ANDRADE, CLEVERTON ROBERTO; DOS SANTOS, JEAN LEANDRO; CHIN, CHUNG MAN. Synthesis and anti-inflammatory intestinal activity of new glucocorticoid derivatives. MEDICINAL CHEMISTRY RESEARCH, v. 29, n. 2 NOV 2019. Web of Science Citations: 0.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MACHADO, Marcella Gabrielle Mendes. Síntese e avaliação anti-inflamatória de derivados esteroides da série Lapdesf GL-FT. 2017. 115 f. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Ciências Farmacêuticas..