Banca de DEFESA: LARISSA AIDA LEMOS DE SOUZA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : LARISSA AIDA LEMOS DE SOUZA
DATE: 27/03/2025
TIME: 09:00
LOCAL: Sessão pública realizada por videoconferência: https://meet.google.com/vgd-wqrn-hbe
TITLE:

EVALUATION OF THE EFFECT OF TRYPSIN INHIBITOR ISOLATED FROM TAMARIND SEEDS ON α-AMYLASE: IN VITRO AND IN SILICO STUDIES

 

KEY WORDS:

Diabetes mellitus; molecular dynamics; molecular docking; protease inhibitors; bioactive peptides

PAGES: 73
BIG AREA: Ciências da Saúde
AREA: Nutrição
SUMMARY:

Type 2 Diabetes Mellitus (T2DM) is one of the main complications resulting from obesity and constitutes a metabolic disorder characterized by persistent hyperglycemia. Considering that alternatives for the control of T2DM are necessary, inhibitors of enzymes involved in the process of carbohydrate digestion may be a possibility for glycemic control in humans. The present study aimed to evaluate the effect of the trypsin inhibitor isolated from tamarind seed (Tamarindus indica L.) (ITT) on α-amylase. After confirmation of the obtaining and characterization of the ITT, the analysis of its in vitro inhibitory activity of ITT against α-amylase was performed. Then, the interaction of the theoretical ITT (ITTp 56/287) and five of its derived peptides with α-amylase, as well as their functional properties, was also evaluated in silico, through Docking and Molecular Dynamics. The Potential Energy of Interaction (EPI), the Free Energy of Binding (ΔGbinding) were also calculated and the main electrostatic, hydrophobic and hydrogen bond interactions of the peptide-α-amylase complex were described by means of three-dimensional representations (stiks). As a result, ITT presented 100% antitryptic activity and a molecular mass of approximately 21 kDa. The results of in vitro inhibition of α-amylase showed an inhibitory activity higher than 37%. These results were corroborated by computational analyses, which showed the strong interaction of the ITTp 56/287 complex and its peptides with the enzyme. The analyses of the Root Mean Square Deviation (RMSD) (up to 0.4 nm) and the Root Mean Square Fluctuation (RMSF) (up to 0.4 nm) showed low flexibility of the tested peptides, i.e., good stability. The EPI analysis showed -705.08 kJ/mol for DTVHDTDGQVPL and -584.11 kJ/mol for TIAPACAPKPAR and the Free Energy of Binding (ΔGbinding) of -308.44 kJ/mol and -245.22 kJ/mol, respectively, confirming the previous results. The peptide sticks highlighted the electrostatic interactions, especially salt bridge, between the main residues that interacted in the complex (DTVHDTDGQVPL, TIAPACAPKPAR e TVSQTPIDIPIGLPVR). In addition, the bioactive potential predicted two candidates with good stability, high half-life and bioactivity in an intestinal simulation environment. In short, according to the sum of findings of this study, the amino acid sequences DTVHDTDGQVPL and TIAPACAPKPAR were revealed as candidates that could, in in vitro and preclinical studies and, later, clinical studies, be tested for action against α-amylase and, consequently, hypoglycemic effect, and could become an alternative in the treatment of DM2.

COMMITTEE MEMBERS:
Presidente - 2578619 - ANA HELONEIDA DE ARAUJO MORAIS
Externa à Instituição - ANNA BEATRIZ SANTANA LUZ - UFRB
Externo ao Programa - 1959889 - DAVI SERRADELLA VIEIRA - nullExterno à Instituição - NORBERTO DE KASSIO VIEIRA MONTEIRO - UFC