Banca de DEFESA: GABRIELA MASTRANGELO GONÇALVES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : GABRIELA MASTRANGELO GONÇALVES
DATE: 02/10/2020
TIME: 13:30
LOCAL: Webconferência
TITLE:

Antinociceptive  and anti-inflammatory profile of hybrid compound: 4-chloro-6- (naphthalen-1-yl) -tetrahydro-2H-pyran-2-yl cis - (±) ) methyl 2- (2- (2,6-dichlorophenylamino) phenyl

KEY WORDS:

nociception, opioid system, inflammation

PAGES: 133
BIG AREA: Ciências Biológicas
AREA: Farmacologia
SUBÁREA: Neuropsicofarmacologia
SUMMARY:

Several drugs currently used have been discovered during experimental and animal observation. Molecular hybridization is a classic strategy of conjugating structures of distinct bioactive compounds into a single molecule, being an effective alternative to rationally architect molecular structures of new compounds. This process is performed in the sense of achieving one of the following objectives: synergism of pharmacological action, dual pharmacological action or modulation of adverse effects. The aim of this study is to evaluate the antinociceptive and anti-inflammatory activities of a new hybrid compound: 4-chloro-6- (naphthalen-1-yl) -tetrahydro-2H-pyran-2-yl cis - (±) ) methyl 2- (2- (2,6-dichlorophenylamino) phenyl) (LS19), obtained by hybridizing the compound [(±) - (2,4,6-cis) -4-chloro-6- (naphthalene-1 2-yl] methanol (CAPIM et al., 2012) with the non-steroidal anti-inflammatory diclofenac. Oral administration of the compound was able to induce antinociceptive activity in models of writhing induced by acetic acid, formalin (both stages) and hot water tail immersion test. To elucidate the mechanism of action of the compound, hot water tail immersion test was used. This model was perform by prior administration of other substances, such as L-NAME (non-selective inhibitor of nitric oxide synthase), 1H- [1,2,4 ] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) (inhibitor of guanylate cyclase sensitive to nitric oxide), and glibenclamide (blocker of the ATP-regulated potassium channels), atropine (muscarinic antagonist), naloxone (selective non-opioid inhibitor), methylnaltrexone, naltrindol and nor-binaltorfimine (selective opioid receptor antagonists of type μ, δ and κ, respectively). The capsaicin-induced nociception model was performed to investigate the role of the mechanism of action of the compound on the TRPV1 receptors, the compound inhibited the nociception induced by capsaicin, which is a TRPV1 receptor agonist, demonstrating involvement of this receptor. The rotarod model was used to evaluate the possibility of interference of the motor performance on the antinociceptive effect, it was demonstrated absence of this interference. As for the anti-inflammatory activity, the result in the paw edema test indicates anti-oedematogenic effect of the compound. There was a decrease in the amount of total leukocytes, indicating that the compound was able to reduce leukocyte migration in the inflammation observed through the air pouch model. In vitro tests will be performed for a more specific analysis of the anti-inflammatory activity of the compound: the quantification of several cytokines IL-1β, TNF-α, IL-6,  IL-4,IL-10 and IFN-γ; determination of nitric oxide concentrations; evaluation of the enzymatic activity of COX-1 and COX-2, showing a selective inhibitory activity of COX-2. The compound was also evaluated for acute and subchronic toxicity, and according to the results, exhibits therapeutic safety.

BANKING MEMBERS:
Externo à Instituição - CARLOS GIOVANI DE OLIVEIRA NASCIMENTO - UNIFAL-MG
Externo à Instituição - GIOVANE GALDINO DE SOUZA - UNIFAL-MG
Presidente - 1674073 - BRUNO GUIMARAES MARINHO
Interno - 3000663 - DAVID DO CARMO MALVAR
Interno - 386960 - WELLINGTON DA SILVA CORTES