Banca de DEFESA: SEVERINO VÍTOR DO NASCIMENTO MOURA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : SEVERINO VÍTOR DO NASCIMENTO MOURA
DATE: 29/07/2025
TIME: 09:00
LOCAL: Auditório do Departamento de Química
TITLE:

IMPROVEMENT OF PLATINUM ANTITUMORAL DRUGS: A STRATEGY TO OVERCOME THE PHENOMENON OF MULTIPLE DRUG RESISTANCE

 

KEY WORDS:

Cancer, chemotherapy, platinum, multidrug resistance (MDR), evolutionary biology.

PAGES: 77
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Inorgânica
SPECIALTY: Química Bio-Inorgânica
SUMMARY:

The phenomenon of multidrug resistance has led to many failures in cancer therapy. Consequently, the development of antineoplastic bioconjugates that can circumvent this phenomenon is necessary. Therefore, the objective of this work is to produce, characterize, evaluate the toxicological aspects, and verify the antitumor activity in an animal model of a new formulation with antineoplastic potential based on oxaliplatin and levan. The synthesis of the platinum precursors, potassium hexachloroplatinate and potassium tetrachloroplatinate, was performed with satisfactory yields (95.6 and 92.3%), and the formation of the compounds was confirmed by X-ray diffraction, with 99.9+% agreement according to their respective crystallographic data. Oxaliplatin was also synthesized using a viable approach, yielding 86.4%. FTIR confirmed the formation of the compound, showing absorption values for the N-H bond stretching at 3209 and 3159 cm-1; C=O and C-O bond stretching at 1658 and 1226 cm-1; and Pt-N bond stretching at 573 cm-1 . 1H and 13C nuclear magnetic resonance data also confirmed the formation of oxaliplatin. X-ray diffractometry also demonstrated the formation of the product, with 99.9+% agreement with its crystallographic chart. Levan was produced, purified, and characterized. 1H and 13C nuclear magnetic resonance data confirmed the presence of the polysaccharide, with five hydrogen signals in their respective chemical shifts and six carbon signals consistent with the furanose ring. The conjugate (SVN7) was formulated with oxaliplatin and oxidized levan in some fructose monomers, enhancing its pharmacological performance. Vibrational spectroscopy evidence reveals the formation of the product, characterized by the presence of C=O and Pt-N bond stretching bands at 1608 and 538 cm-1, as well as the N-H bond bending band at 1510 cm-1. The acute oral toxicity study in an animal model followed the OECD 423 protocol, classifying the platinum conjugate SVN7 as category 5, indicating low toxicity, with an LD50 greater than 2000 mg kg-1. Furthermore, liver toxicity parameters (AST and ALT) were also monitored, revealing that the tested composition does not induce liver damage. The antitumor activity study in an animal model was also performed in male Swiss mice inoculated with Ehrlich carcinoma. The results demonstrated high efficacy of the tested formulation, with 94% inhibition of tumor mass. The animal model assays proved accurate, demonstrating the therapeutic potential of the platinum conjugate in cancer therapy.

COMMITTEE MEMBERS:
Externo à Instituição - EDUARDO CARVALHO LIRA
Interno - JOAO RUFINO DE FREITAS FILHO
Presidente - MONICA FREIRE BELIAN