Banca de QUALIFICAÇÃO: BARBARA FERNANDA PESSOA DE ANDRADE

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : BARBARA FERNANDA PESSOA DE ANDRADE
DATE: 28/11/2022
TIME: 10:00
LOCAL: Goole meet
TITLE:

Determination of tumor cell death pathways of the mesoionic compound 5-(4-chlorophenyl)-3-methyl-4-phenyl-1,3-thiazolium-2-thiolate (MI-2) in the Acute Promyelocytic Leukemia (HL) tumor cell line -60)

KEY WORDS:

Mesoionic; Antitumor; Leukemia; Cell Death; Mechanism of Action.

PAGES: 40
BIG AREA: Ciências Agrárias
AREA: Medicina Veterinária
SUBÁREA: Clínica e Cirurgia Animal
SPECIALTY: Farmacologia e Terapêutica Animal
SUMMARY:

Cancer is a cosmopolitan disease marked by deregulation of the cell cycle, which favors the proliferation of altered cells and the development of metastases. According to the WHO, it is among the leading causes of death in the world, being a public health issue. Thus, the search for new therapeutic possibilities that are effective and less toxic to patients has gained space in scientific research. Mesoionic compounds are heterocyclic chemical compounds with 5-atom rings and great structural variety. They are essentially synthetic but present naturally occurring rings such as thiazole and present a wide range of biological activities reported in the scientific environment and which have been widely tested for their antitumor potential in several carcinogenic strains. Based on the results associated with mesoionics described in the literature, in this work the derivative 5-(4-chlorophenyl)-3-methyl-4-phenyl-1,3-thiazolium-2-thiolate (MI-2) is studied for the lineage of Acute Promyelocytic Leukemia (HL-60) regarding its antitumor potential and the main pathways of action mechanism in 72h Cell viability tests were performed through MTT, morphological analysis with HE staining, DNA fragmentation analysis through the DNA ladder test, cytotoxicity in mononuclear cells (PBMC) by MTT test, apoptosis/necrosis test by Annexin V and the membrane potential assay by rhodamine 123. The results obtained indicated that MI-2 presented cytotoxicity after exposure to 72h to the drug in the HL-60 strain, with growth inhibition potential above 70% in the single dose test (25μg/mL) and dose below 4μg/mL for the calculation of the mean inhibitory concentration (IC50), low toxicity in rat lymphocytes. In addition, tests were performed indicating the induction of cell death pathways, such as morphological analysis and DNA fragmentation, which suggest that the mesoionic derivative is capable of inducing death by apoptotic and autophagic pathways. The mitochondrial depolarization assay has so far demonstrated that there was a dose-dependent depolarization of the membrane, especially at a concentration of 12μg/ml. These results indicated that the compound MI-2 has antitumor activity in HL-60 cells, however, further tests to deepen the mechanisms of action are being carried out to confirm the anticancer potential of the mesoionic derivative MI-2.

BANKING MEMBERS:
Presidente - EMMANUEL VIANA PONTUAL
Externa à Instituição - SANDRINE MARIA DE ARRUDA LIMA - UFPE
Externa à Instituição - NATALIE EMANUELLE RIBEIRO RODRIGUES - UPE