Banca de DEFESA: ÉRIKA GEICIANNY DE CARVALHO MATIAS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ÉRIKA GEICIANNY DE CARVALHO MATIAS
DATE: 24/01/2025
TIME: 09:00
LOCAL: Sala Carl Peter von Dietrich e videoconferência
TITLE:

QUANTUM BIOCHEMISTRY APPROACH APPLIED TO THE MODULATION OF SIRT6 AND PIM1: UNVEILING NEW THERAPEUTIC STRATEGIES WITH FLAVONOIDS

KEY WORDS:

SIRT6, PIM1, Modulators, Metabolic Diseases, Cancer, Molecular Modeling, MFCC, DFT

PAGES: 98
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Metabolic diseases and cancers affect millions of people worldwide, representing a health and well-being problem for society. In this scenario, two proteins, SIRT6 and PIM1, emerge. These macromolecules have stood out as potential therapeutic targets for these pathologies since their regulatory functions are directly associated with preventing these diseases. SIRT6 is an NAD+-dependent deacylase, and its activation has potential against metabolic and aging-related diseases. In contrast, its inhibition is considered promising in cancer therapy. The investigation of the modulation of this protein by specific molecules stands out as a promising area. PIM1 is a proto-oncogene overexpressed in several types of human cancer, and its inhibition is considered a promising target for cancer therapy. Here, we explore the modulation of SIRT6 with the flavonoids quercetin (QUE) and its derivative isoquercetin (ISO), in addition to catechin gallate (GC) and trichostanin-A (TSA), as well as the PIM1 protein with the flavonoids quercetin (QUE), myricetin (MYC) and pentahydroxyflavone (PTH), providing a detailed view of the molecular interactions that lead to the activation and/or inhibition of these proteins. For this, we used computational methods from the perspective of Molecular Modeling through the Molecular Fractionation with Conjugated Caps (MFCC) technique in accordance with the calculation parameters of the Density Functional Theory (DFT). These evaluations were carried out within a radius of up to 10.0 Å away from the modulators. The energy analysis of the SIRT6-modulator complex demonstrated that the activating substances (GC) and (TSA) were more expressive compared to the inhibitory molecules (QUE) and (ISO). In contrast, for the PIM1-inhibitor complex, the flavonoid that presented the most expressive interaction was (PTH) followed by (QUE) and (MYC). Our results provide relevant evidence for the development of therapeutic strategies targeting SIRT6 and PIM1, which have the potential to impact the regulation of these proteins and open new perspectives in the research of treatments for metabolic diseases and cancer.

COMMITTEE MEMBERS:
Externo à Instituição - DOUGLAS SOARES GALVAO - UNICAMP
Interno - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Externa à Instituição - KATYANNA SALES BEZERRA - UNICAMP
Externo à Instituição - LUIZ ANTONIO RIBEIRO JUNIOR - UnB
Presidente - 1352009 - UMBERTO LAINO FULCO