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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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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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Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior - Brasil (CAPES)–Finance Code 001.

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Authors and Affiliations

  1. Laboratório de Biotecnologia do Câncer, Programa de Pós-Graduação em Biotecnologia (PPGB), Centro de Desenvolvimento Tecnológico (CDTec), Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, 96010-900, Brazil

    Mariana S. Sonego, Natália V. Segatto, Lucas Damé, Thais Larré Oliveira, Fabiana Kömmling Seixas & Tiago Collares

  2. Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Desenvolvimento Tecnológico (CDTec), Universidade Federal de Pelotas, Pelotas, RS, 96010-900, Brazil

    Mariana Fronza & Lucielli Savegnago

  3. Laboratório de Síntese Orgânica Limpa (LASOL), CCQFA, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, 96010-900, Brazil

    Carolina B. Gomes & Diego Alves

  4. Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA

    Kyle M. Schachtschneider

  5. Department of Biochemistry & Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA

    Kyle M. Schachtschneider

  6. National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Kyle M. Schachtschneider

Authors
  1. Mariana S. Sonego
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  2. Natália V. Segatto
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  3. Lucas Damé
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  4. Mariana Fronza
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  5. Carolina B. Gomes
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  9. Kyle M. Schachtschneider
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  10. Diego Alves
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  11. Tiago Collares
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Contributions

Material preparation, data collection and analysis were performed by Mariana S. Sonego, Natália V. Segatto, Lucas Damé, Mariana Fronza, Carolina B. Gomes, Thais Larré Oliveira. Study conception and design were supervised by Fabiana Kömmling Seixas, Lucielli Savegnago, Kyle M. Schachtschneider, Diego Alves and Tiago Collares. The first draft of the manuscript was written by Mariana S. Sonego and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Tiago Collares.

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Sonego, M.S., Segatto, N.V., Damé, L. et al. 7-Chloroquinoline-1,2,3-triazoyl carboxamides induce cell cycle arrest and apoptosis in human bladder carcinoma cells. Invest New Drugs 38, 1020–1030 (2020). https://doi.org/10.1007/s10637-019-00861-w

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