• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.75.2020.tde-11012021-174206
Document
Author
Full name
Katarina Botelho Saraiva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2020
Supervisor
Committee
Leitão, Andrei (President)
Araújo, Heloisa Sobreiro Selistre de
Machado Neto, João Agostinho
Title in Portuguese
Análise da atividade de moléculas inibidoras de cisteíno protease em linhagens celulares de câncer de próstata (PC-3 e DU 145) e fígado (Hep G2)
Keywords in Portuguese
atividade citotóxica e citostática
câncer de fígado
câncer de próstata
estudo fenotípico
inibidores de cisteíno protease
peptoides de nitrila
Abstract in Portuguese
O câncer refere-se a doenças que possuem em comum o aumento incontido de células, que podem migrar para diversas regiões do organismo, tendo relação com aproximadamente 1 a cada 6 mortes causadas no mundo. As cisteíno catepsinas humanas são alvos estudados em neoplasias, uma vez que estão envolvidas no desenvolvimento tumoral. Peptideomiméticos que contêm o grupo nitrila apresentam inibição para cisteíno catepsinas e apresentam potencial atividade citotóxica e citostática. No entanto, é necessário um estudo mais detalhado dos perfis bioativos destes compostos em busca de alternativas terapêuticas para os diversos tipos de câncer. Neste trabalho, uma triagem foi realizada para cerca de 50 compostos sintetizados no grupo (NEQUIMED) usando nos ensaios as linhagens celulares de câncer de próstata (DU 145 e PC-3) e fígado (Hep G2) e comparadas com células não tumorais de fibroblasto de camundongo BALB/3T3 clone A31. As substâncias mais promissoras foram avaliadas em ensaios subsequentes para avaliar a atividade citotóxica e citostática. A série de peptoides de nitrila apresentou uma maior potência citostática para os compostos Neq0995 e Neq0994 nas linhagens de câncer de próstata. Já para a linhagem de hepatocarcinoma, os melhores compostos foram o Neq0994, e o Neq1014. A relação estrutura-atividade demonstrou que grupos volumosos são importantes na posição P3 (bifenila) para ambas linhagens celulares, sendo que a ciclopropila pode estar presente como substituinte em P1 somente para a linhagem de hepatocarcinoma (Hep G2).
Title in English
Analysis of the activity of cysteine protease inhibitory molecules in cellular lines of prostate cancer (PC-3 and DU 145) and liver cancer (Hep G2)
Keywords in English
cysteine protease inhibitors
cytotoxic and cytostatic activity
liver cancer
nitrile peptides
phenotypic study
prostate cancer
Abstract in English
Cancer refers to diseases that have in common the uncontrolled increase of cell number, which can migrate to different regions of the body. Cancer leads to 1 in 6 deaths, approximately, in the world. Human cysteine cathepsins are targets studied in neoplasia since they are involved in tumor development. Peptidomimetic compounds containing the nitrile group are cysteine cathepsin inhibitions with potential cytotoxic and cytostatic activity. However, it is necessary to perform more in depth-studies to define the biological profile for these compounds, aiming to identify therapeutic alternatives for cancer. Here, a screening was performed for 50 compounds synthesized in the group using prostate (DU 145 and PC-3) and liver (Hep G2) cancer cell lines. A comparative analysis was also made between these tumoral cells and the non-tumoral mouse fibroblast cells (BALB/3T3 clone A31). The most promising substances were evaluated in subsequent trials to assess the cytotoxic and cytostatic activities. The series of nitrile peptoids showed a better cytostatic potency, being Neq0995 and Neq0994 compounds the most potent for both prostate cancer lineages. The best compounds for the hepatocarcinoma cells were Neq0994 and Neq1014. The structure-activity relationship demonstrated that large groups (like biphenyl) are important in the P3 position for both cell lines. In contrast, the cyclopropyl substitution in the P1 position is tolerated only for the hepatocarcinoma cell line (Hep G2).
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2021-01-12
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2022. All rights reserved.