Banca de DEFESA: GABRIEL CHRISTIAN DE FARIAS MORAIS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : GABRIEL CHRISTIAN DE FARIAS MORAIS
DATE: 26/11/2024
TIME: 08:30
LOCAL: Videoconferência - Link para acesso: meet.google.com/mku-mcmr-jka
TITLE:

ADMET and Quantum Biochemistry Predictions of Bioactives with Antimicrobial or Neuroactive Potential

KEY WORDS:

Molecular Modeling; ADMET Predictions; Quantum Biochemistry; Neuroactive Bioactives; Antimicrobial Bioactives; Chagas Disease

PAGES: 85
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

The increasing demand for novel neuroactive and antimicrobial drugs motivated this study to conduct ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions and quantum biochemical analyses of bioactive compounds with eugeroic (modafinil), noradrenergic (atomoxetine), antiviral (tecovirimat), and antiparasitic (BZTS) activities. Advanced computational tools such as ADMETlab 2.0, admetSAR, FAFDrugs4, MolInspiration, SwissADME, ADMET-AI, pkCSM, and PRED-HERG were utilized to evaluate the pharmacokinetic and toxicological profiles of Modafinil, Atomoxetine, and Tecovirimat, identifying risks such as hepatotoxicity, cardiotoxicity, and mutagenic potential. The focus then shifted to Chagas disease, selecting six compounds with antichagasic potential, with BZTS emerging as a standout due to its favorable ADMET profile and low toxicity risk, meeting all medicinal chemistry guidelines. Molecular modeling studies and Density Functional Theory (DFT) calculations revealed robust and specific interactions between BZTS and cruzain, a key Trypanosoma cruzi enzyme, indicating stability and high affinity within the ligand-receptor complex through interactions with amino acids GLU208 (-10.2 kcal/mol), MET68 (-4.75 kcal/mol), LEU67 (-4.08 kcal/mol), ASN69 (-3.68 kcal/mol), LEU160 (-3.38 kcal/mol), ALA138 (-1.98 kcal/mol), GLU117 (-1.97 kcal/mol), and ASP161 (-1.68 kcal/mol). Additionally, frontier orbital analyses (HOMO -5.85 eV, LUMO -3.37 eV) and quantum chemical descriptors—ionization potential (5.85 eV), electron affinity (3.37 eV), chemical hardness (1.24 eV), softness (0.81 eV), chemical potential (-4.61 eV), electronegativity (4.61 eV), and electrophilicity (13.19 eV)—confirmed the BZTS compound’s potential for effective biological target interactions, reinforcing its therapeutic potential. This study underscores the effectiveness of in silico methodologies in identifying and characterizing promising bioactive compounds, with BZTS emerging as a promising candidate for Chagas disease treatment. Integrating computational predictions in drug development proves crucial for accelerating the discovery and optimization of safer, more effective drugs, significantly contributing to advances in pharmacology and public health.

COMMITTEE MEMBERS:
Presidente - 2985070 - JONAS IVAN NOBRE OLIVEIRA
Interno - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Externa à Instituição - JÉSSICA DE FÁTIMA VIANNA - UERN