Author | Barros, Francisco Washington Araujo | |
Author | Bezerra, Daniel Pereira | |
Author | Ferreira, Paulo Michel Pereira | |
Author | Cavalcanti, Bruno Coelho | |
Author | Silva, Teresinha Gonçalves da | |
Author | Pitta, Marina Galdino da Rocha | |
Author | Lima, Maria do Carmo Alves de | |
Author | Galdino, Suely L | |
Author | Pitta, Ivan da Rocha | |
Author | Lotufo, Letícia Veras Costa | |
Author | Moraes Filho, Manoel Odorico de | |
Author | Burbano, Rommel Mario Rodríguez | |
Author | Guecheva, Temenouga Nikolova | |
Author | Henriques, João Antonio Pegas | |
Author | Pessoa, Cláudia do Ó | |
Access date | 2017-08-28T18:45:32Z | |
Available date | 2017-08-28T18:45:32Z | |
Document date | 2013 | |
Citation | BARROS, F. W. A. et al. Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives. Toxicology and Applied Pharmacology, v. 268, p. 37–46, 2013. | pt_BR |
ISSN | 0041-008X | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/20786 | |
Description | Bezerra, Daniel Pereira “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. | pt_BR |
Sponsorship | Brazilian National Research Council, National Institute of Science and Technology for Pharmaceutical Innovation
(CNPq/RENORBIO/INCT-IF) and INCT-Bioanalítica | pt_BR |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Acridinas | pt_BR |
Subject in Portuguese | Tiazolidinas | pt_BR |
Subject in Portuguese | Tiazacridina | pt_BR |
Subject in Portuguese | DNA Topoisomerase I | pt_BR |
Subject in Portuguese | Apoptose | pt_BR |
Title | Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.taap.2013.01.010 | |
Abstract | Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione - AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione - AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl)-1,3-thiazolidine-2,4-dione - AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2,4-dione - AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin-eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways. | pt_BR |
Affilliation | Federal University of Ceará. School of Medicine. Department of Physiology and Pharmacology. Fortaleza, CE, Brazil | pt_BR |
Affilliation | Federal University of Sergipe. Department of Physiology. São Cristóvão, SE, Brazil | pt_BR |
Affilliation | Federal University of Piauí. Department of Biological Sciences. Picos, PI, Brazil | pt_BR |
Affilliation | Federal University of Ceará. School of Medicine. Department of Physiology and Pharmacology. Fortaleza, CE, Brazil | pt_BR |
Affilliation | Federal University of Pernambuco. Department of Antibiotics. Recife, PE, Brazil | pt_BR |
Affilliation | Federal University of Pernambuco. Department of Antibiotics. Recife, PE, Brazil | pt_BR |
Affilliation | Federal University of Pernambuco. Department of Antibiotics. Recife, PE, Brazil | pt_BR |
Affilliation | Federal University of Pernambuco. Department of Antibiotics. Recife, PE, Brazil | pt_BR |
Affilliation | Federal University of Pernambuco. Department of Antibiotics. Recife, PE, Brazil | pt_BR |
Affilliation | Federal University of Ceará. School of Medicine. Department of Physiology and Pharmacology. Fortaleza, CE, Brazil | pt_BR |
Affilliation | Federal University of Ceará. School of Medicine. Department of Physiology and Pharmacology. Fortaleza, CE, Brazil | pt_BR |
Affilliation | Federal University of Pará. Institute of Biological Sciences. Belém, PA, Brazil | pt_BR |
Affilliation | Federal University of Rio Grande do Sul. Biotechnology Center. Porto Alegre, RGS, Brazil | pt_BR |
Affilliation | Federal University of Rio Grande do Sul. Biotechnology Center. Porto Alegre, RGS, Brazil | pt_BR |
Affilliation | Federal University of Ceará. School of Medicine. Department of Physiology and Pharmacology. Fortaleza, CE, Brazil | pt_BR |
Subject | Acridine | pt_BR |
Subject | Thiazolidine | pt_BR |
Subject | Thiazacridine | pt_BR |
Subject | DNA topoisomerase I | pt_BR |
Subject | Apoptosis | pt_BR |