Banca de DEFESA: GABRIEL FREITAS DO RIO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : GABRIEL FREITAS DO RIO
DATE: 10/12/2024
TIME: 13:00
LOCAL: https://conferenciaweb.rnp.br/sala/carlos-mauricio-rabello-de-santanna
TITLE:

EVALUATION OF THE INTERACTION BETWEEN NEW TRYPANOCIDE 1,2,4--TRIAZOLE-3-THIONES WITH HUMAN SERUM ALBUMIN

KEY WORDS:

Trypanosoma cruzi, Piperine derivatives, spectroscopic methods, Human serum albumin, molecular docking

PAGES: 203
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Fotoquímica Orgânica
SUMMARY:

There is a strong demand for the development of new drugs for the treatment of Chagas disease, a neglected tropical disease. This work investigates the interaction of human serum albumin (HSA) with a novel series of piperine-derived 1,2,4-triazole-3-thiones (19b, 19c, 19d and 19e), which have been shown by our group to exhibit trypanocidal activity in the low micromolar range. The study was performed by spectroscopic techniques, including UV-vis absorption, circular dichroism, steady-state and time-resolved fluorescence combined with theoretical calculations (molecular docking). The interaction of all compounds was spontaneous (ΔG◦ < 0) and strong (K_a ≈ 10⁵ M^-1), resulting in an unconventional ground-state association (there is a combination of static and dynamic quenching mechanisms). The positive ΔH◦ and ΔS◦ values are indicative that the interaction between the compounds and HSA is entropically driven and suggest that it is predominantly governed by hydrophobic interactions. Interestingly, the competitive interaction results show that the compounds containing a cyclohexyl substituent at N4 (19c and 19e) bind preferentially to Sudlow site I, while the compounds containing a phenylethyl substituent at N4 (19b and 19d) bind preferentially to Sudlow site II. The docking results indicate that the interaction profiles of 19c and 19e with Sudlow site I are quite similar, as are those of 19b and 19d with Sudlow site II. In all cases, the interactions evidenced by the theoretical method are predominantly hydrophobic, in agreement with the thermodynamic data. Favorable interaction profiles with HSA should have a positive effect on the pharmacokinetics of piperine-derived trypanocidal compounds and probably a major influence on their in vivo efficacy.

COMMITTEE MEMBERS:
Presidente - 1220404 - CARLOS MAURICIO RABELLO DE SANT ANNA
Interno - 2624418 - CLAUDIO EDUARDO RODRIGUES DOS SANTOS
Interna - 1177598 - ROSANE NORA CASTRO
Externa à Instituição - NELILMA CORREIA ROMEIRO - UFRJ
Externo à Instituição - RODRIGO JOSÉ CORREA - UFRJ