Banca de QUALIFICAÇÃO: RAYANI ALMEIDA DE LIMA
Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.DISCENTE : RAYANI ALMEIDA DE LIMA
DATA : 16/03/2020
HORA: 14:00
LOCAL: sala 306, 3º andar, Bloco B, Campus SA da Fundação Universidade Federal do ABC, localizada na Avenida dos Estados, 5001, Santa Terezinha, Santo André, SP
TÍTULO:
Hydrolytic stability and anti-inflammatory properties of a betalain derived from mefenamic acid
PÁGINAS: 40
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Orgânica
ESPECIALIDADE: Físico-Química Orgânica
RESUMO:
Inflammation can be defined as a natural defense response of the organism triggered by noxious stimuli, such as infection by microorganisms or tissue damage. Diphenylamine derivatives, such as diclofenac and mefenamic acid, are used as nonsteroidal anti-inflammatory drugs due to their ability to prevent prostaglandin biosynthesis by inhibiting the activity of cyclooxygenases COX-1 and COX-2. Despite their therapeutic effectiveness, the use of these drugs is limited by their side effects, mainly due to their tendency to increase the occurrence of gastroduodenal ulcers. Research has been carried out to find new therapeutic drugs for a variety of inflammatory diseases. Betalains are non-toxic pigments found in plants and fungi that interfere in the pro-inflammatory signaling cascade, mainly in the nuclear factor kappa B (NF-κB) pathway, which acts in the transcription of genes helping to regulate the inflammatory response. Diphenylbetalains are non-natural betalains that have greater hydrolytic stability compared to their monosubstituted analogues. In this master's project, it was proposed the semisynthesis of a betalain derived from the coupling between betalamic acid and mefenamic acid, a commercial diphenylamine used as a non-steroidal anti-inflammatory drug. The product obtained was called mefenylbetalain (mefBeet) and its capacity to inhibit the action of NF-κB and COXs will be determined. Semisynthesis was carried out using betalamic acid (HBt) and mefenamic acid in acidified ethyl acetate, a benign organic solvent, resulting in an orange solid that was purified and characterized by NMR and mass spectrometry. MefBeet is soluble in water and its hydrolysis does not depend on the pH in the range of 3 to 7. Low absorption and bioavailability are some problems found in compounds with low water solubility, such as mefenamic acid (~0.004 mg/ml at 37 °C). Water solubility of mefBeet suggests the need for a lower dosage of the compound to obtain its therapeutic concentration, since it would be better dissolved in the fluids of the gastrointestinal tract. The maximum absorption of mefBeet in water is 502 nm and its excitation at that wavelength produces an emission centered at 567 nm (Stoke shift: 65 nm, 2284 cm– 1). Although the quantum fluorescence yield in the solution is low (ΦFL = 3.72 × 10–3), betalains tend to become very fluorescent in the presence of proteins, and their intracellular behavior can be monitored by fluorescence microscopy, another advantage compared to mefenamic acid, which mechanism of action is not completely understood yet. The results should contribute to the development of anti-inflammatory drugs with combined action obtained from renewable sources.
MEMBROS DA BANCA:
Presidente - Interno ao Programa - 250.887.078-19 - ERICK LEITE BASTOS - USP
Membro Titular - Examinador(a) Interno ao Programa - 1600860 - ALVARO TAKEO OMORI
Membro Titular - Examinador(a) Interno ao Programa - 1939561 - FERNANDO HEERING BARTOLONI
Membro Suplente - Examinador(a) Interno ao Programa - 1544379 - ANDERSON ORZARI RIBEIRO