Banca de DEFESA: DANIELA DA COSTA TRISTÃO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : DANIELA DA COSTA TRISTÃO
DATE: 17/05/2023
TIME: 09:00
LOCAL: https://conferenciaweb.rnp.br/sala/daniela-95
TITLE:

COMPARATIVE EVALUATION OF THE ANTI-TRIPANOSOMA, ANTI-LEISHMANIA AND ANTI-TUMOR ACTIVITY OF THE APOPHINE ALKALOID DICENTRINE OBTAINED FROM Ocotea puberula (Rich. Nees) AND DERIVATIVES

PAGES: 105
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Química dos Produtos Naturais
SUMMARY:

Chagas Disease and Visceral Leishmaniasis are serious neglected tropical diseases caused, respectively, by the protozoa Trypanosoma cruzi and Leishmania (L.) infantum. Together, they accumulate 100,000 annual cases, mainly affecting vulnerable populations in developing countries. Considering its lethality and the important toxicity problems associated with current treatments, it is urgent to search for new active substances against these diseases. With regard to cancer, which is the second leading cause of death in the world, prospecting for new chemotherapy is essential. Specifically, chemotherapy is one of the main treatment strategies for head and neck cancer, aiming at curing and preserving the functionality of the affected organs. In this context, and based on the premise that special metabolites derived from plants are an inexhaustible source of bioactive substances, the present work presents a comparative study of anti-T.cruzi, anti-L. (L.) infantum and antitumoral among the aporphine alkaloid (S)-dicentrine, obtained from O. puberula, and three derivatives: (S)-N-methyldicentrine (1), (6aS, 6S)-dicentrine N-oxide (2) and (6aS, 6R)-dicentrine N-oxide (3), the latter being a novel compound. The four aporphines were obtained and characterized by spectroscopic and spectrometric techniques. The N-oxide derivative (2) was the most active against the amastigote form of T. cruzi, (CE50 = 9.9 µM and SI > 20.2; benznidazole: CE50 = 6.5 µM and SI > 30.7), indicating improvement on the activity and selectivity of the starting alkaloid. Against the amastigote form of L. (L.) infantum, N-oxide (3) was the most active derivative (EC50 = 34.5 µM; miltefosine = 10.2 µM; (S)-dicentrine = 10.3 µM), showing better SI than its precursor (SI > 5.8; (S)-dicentrine = 5). Against the SCC-143 and SCC-154 tumor cell lines, associated with head and neck cancer, the starting alkaloid was more active (IC50 = 7,1 and 20,0 µM, respectively; cisplatin = 3,6 and 0,8 µM). In general, N-oxidation showed to be a more promising functionalization than N-methylation, generating more active and less toxic compounds in the biological models studied. In addition, the stereochemistry of these derivatives was presented as an essential characteristic for the expression of activity.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1623577 - JOAO HENRIQUE GHILARDI LAGO
Membro Titular - Examinador(a) Externo à Instituição - WALMIR SILVA GARCEZ - UFMS
Membro Titular - Examinador(a) Externo à Instituição - MARCOS PIVATTO - UFU
Membro Suplente - Examinador(a) Interno ao Programa - 1544379 - ANDERSON ORZARI RIBEIRO
Membro Suplente - Examinador(a) Externo à Instituição - EDGARD ANTONIO FERREIRA - UPM