Banca de DEFESA: COSME HENRIQUE COÊLHO DOS SANTOS DE OLIVEIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : COSME HENRIQUE COÊLHO DOS SANTOS DE OLIVEIRA
DATE: 28/08/2023
TIME: 10:00
LOCAL: Sala 50 do PPGQ
TITLE:

SPECTROSCOPIC STUDY OF THE INTERACTION OF COMPOUNDS
BIOACTIVES WITH HUMAN SERUM ALBUMIN (ASH)

KEY WORDS:

HUMAN SERUM ALBUMIN (ASH), flowering, bioactive compounds

PAGES: 221
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

Spectroscopic studies were carried out for the interaction of bioactive compounds from the classes of thiosemicarbazones (UTS, DFTS and TFTS), metformins (MFCl, MFBr and MFCF3), chalcone (IC9) and xanthones (1MXT, 2MXT, 4MXT, 23MXT and 34MXT) with human serum albumin (ASH). Through fluorescence spectroscopy studies, it was found that all thought bioactive compounds interact with ASH in the ground state through a static fluorescence discharge mechanism, which is indicated by the decrease in KSV values with increasing temperature, as well as kq values of the order of 1013 M -1 s -1 . The values of the association constant (Ka) for all observed cases were of the order of 104 M −1, showing a moderate interaction of those compounds with ASH and the results of circular dichroism (DC) indicated a weak disturbance in the secondary structure of albumin after the interaction with the ligand. Thermodynamic parameters for thiosemicarbazones suggest that the binding process is controlled entropically (ΔS° between 0.022 and 0.072 J/mol.K) and enthalpically (ΔH° between -32.3 and -4.9 kJ/mol), with values compatible Gibbs free energy change (ΔG° between -39 and -24 kJ/mol). The interaction between each halogenated metformin and ASH is spontaneous (ΔG° between -28 and -26 kJ/mol) and entropically conducted (ΔS° between 0.120 and 0.147 J/mol.K) with an enthalpically unfavorable interaction (ΔH° between 9.48 and 18.5 kJ/mol). For the interaction between chalcone IC9 and ASH, the thermodynamic parameters indicate a spontaneous interaction with compatible Gibbs free energy (ΔG° = -27.9 kJ/mol) that is both enthalpically driven (ΔH° = -20.8 kJ/mol) and entropically (ΔS° = 0.023 J/mol.K) For the interaction between xanthones and ASH, the thermodynamic parameters suggest that the binding process is attended entropically (ΔS° between 0.008 and 0.068 J/mol.K) and enthalpically ( ΔH° between -25.5 and -7.2 kJ/mol), with compatible Gibbs free energy change values (ΔG° between -28.2 and -27.3 kJ/mol). Competitive binding experiments in the presence of warfarin, ibuprofen and digitoxin site markers suggest that thiosemicarbazones UTS, DFTS and TFTS compete for the same warfarin binding site, indicating Sudlow's I site as the main binding site. Competitive binding studies for MFCl, MFBr and MFCF3 in the presence of warfarin, ibuprofen or digitoxin also indicated the Sudlow I site as the main binding site. There is only one major binding site for IC9, which is located at Sudlow site I. For 1MXT, 2MXT, 4MXT, 23MXT, and 34MXT, competitive binding experiments in the presence of site markers warfarin, ibuprofen, and digitoxin suggest that monomethoxylated compounds prefer to complex at the Sudlow I site, while dimethoxylated compounds have a greater tendency toward complexation with Sudlow site II.

COMMITTEE MEMBERS:
Interno - 1220404 - CARLOS MAURICIO RABELLO DE SANT ANNA
Presidente - ***.460.177-** - JOSE CARLOS NETTO FERREIRA - UFRRJ
Externo à Instituição - JOSUÉ SEBASTIAN BELLO FORERO - UFRJ
Interno - 1058758 - MARCO EDILSON FREIRE DE LIMA
Externo à Instituição - RODRIGO JOSÉ CORREA - UFRJ