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06.11.2019 | PRECLINICAL STUDIES

7-Chloroquinoline-1,2,3-triazoyl carboxamides induce cell cycle arrest and apoptosis in human bladder carcinoma cells

verfasst von: Mariana S. Sonego, Natália V. Segatto, Lucas Damé, Mariana Fronza, Carolina B. Gomes, Thais Larré Oliveira, Fabiana Kömmling Seixas, Lucielli Savegnago, Kyle M. Schachtschneider, Diego Alves, Tiago Collares

Erschienen in: Investigational New Drugs | Ausgabe 4/2020

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Summary

In the present study, the antitumoral properties of a series of 7-chloroquinoline-1,2,3-triazoyl-carboxamides (QTCA) were investigated by analyzing their cytotoxic activities against human bladder cells (5637; grade II carcinoma). In addition, their effects on cell viability, cell cycle arrest mechanisms, apoptosis induction, in silico molecular docking, and detection of pro-apoptotic and anti-apoptotic proteins were evaluated. The cytotoxicity assay identified major dose- and time-dependent cytotoxic effects in 5637 cells after they were exposed to treatment with QTCA, only minimal effects were observed on normal cells. A live/dead assay confirmed that significant cell death, arrest in the G0/G1 phase and apoptosis were associated with treatment by 1-(7-Chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) and 1-(7-Chloroquinolin-4-yl)-N-(4-fluorophenyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide (QTCA-4). The in silico results indicated that these compounds acted through different mechanisms for the induction of cell cycle arrest and apoptosis. Western blotting confirmed the binding of the QTCAs to pro- and anti-apoptotic proteins. In conclusion, QTCA-1 and QTCA-4 are promising candidates for inducing cytotoxicity, cell cycle arrest, and apoptosis in human bladder cancer cells.

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Titel: 7-Chloroquinoline-1,2,3-triazoyl carboxamides induce cell cycle arrest and apoptosis in human bladder carcinoma cells
verfasst von: Mariana S. Sonego
Natália V. Segatto
Lucas Damé
Mariana Fronza
Carolina B. Gomes
Thais Larré Oliveira
Fabiana Kömmling Seixas
Lucielli Savegnago
Kyle M. Schachtschneider
Diego Alves
Tiago Collares
Publikationsdatum: 06.11.2019
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 4/2020
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00861-w

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7-Chloroquinoline-1,2,3-triazoyl carboxamides induce cell cycle arrest and apoptosis in human bladder carcinoma cells

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