Synthesis and antitubercular evaluation of 7-chloro-4-alkoxyquinoline derivatives

Authors

  • Marcelle de Lima Ferreira Bispo Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil.
  • Laura Nogueira de Faria Cardoso Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil.
  • Maria C. S. Lourenço Fundação Oswaldo Cruz, Instituto de Pesquisas Clínicas Evandro Chagas, Departamento de Bacteriologia, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, Brazil
  • Flávio Augusto Ferreira Martins Bezerra Fundação Oswaldo Cruz, Instituto de Pesquisas Clínicas Evandro Chagas, Departamento de Bacteriologia, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, Brazil
  • Rodrigo Pedro Pinto Soares Pinto Soares Fundação Oswaldo Cruz, Centro de Pesquisas René Rachou, Laboratório de Biomarcadores de Diagnóstico e Monitoração, Av. Augusto de Lima, 1715, Barro Preto, 30190-002, Belo Horizonte, MG, Brazil
  • Caryne Margotto Bertollo Fundação Oswaldo Cruz, Centro de Pesquisas René Rachou, Laboratório de Biomarcadores de Diagnóstico e Monitoração, Av. Augusto de Lima, 1715, Barro Preto, 30190-002, Belo Horizonte, MG, Brazil
  • Marcus Vinícius Nora de Souza Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil

DOI:

https://doi.org/10.13171/mjc.4.1.2015.19.02.10.18/desouza

Abstract

A series of eight 7-chloro-4-alkoxyquinoline derivatives (2a-h) have been synthesized and their in vitro (antimycobacterial) activity against Mycobacterium tuberculosis was evaluated.  Furthermore, all the active compounds were selected for evaluation of their cytotoxicities against the human hepatoma (HepG2) and the relative selectivity (selective index) of these compounds against M. tuberculosis compared to HepG2 was calculated based on MLD50/MIC ratios.  These biological results have been compared to a series of 7-chloro-4-aminoquinoline derivatives 1a-i, previously identified by our research group with the aim to provide important information about the structure-activity relationship of quinoline derivatives.

References

- WHO Global TB report 2011: http://www.who.int/tb/publications/global_report/en/ (Accessed: February, 10, 2015).

- A. L. P. Candéa, M. L. Ferreira, K. C. Pais, L. N. F. Cardoso, C. R. Kaiser, M. G. M. O. Henriques, M. C. S. Lourenço, F. A. F. M. Bezerra, M. V. N. de Souza. Bioor. Med. Chem. Lett., 2009, 19, 6272-6274.

- S. S. Ravichandran; S. A. Dhanaraj; H. Rajak; S. Kumar. W.J.P.P.S., 2014, 3, 1072-1082.

- N. D. Heindel, S. A. Fine. J. Heterocycl. Chem., 1969, 6, 961.

- L. R. Gomes, J. N. Low, J. L. Wardell, L. N. F. Cardoso, M. V. N. De Souza, Acta Crystallogr., Sect. C: Cryst. Struct. Commun., 2013, 69, 191-194.

- F. Denizot, R. Lang. J. Immunol. Meth., 1986, 89, 271-277.

- J. Canetti, E. Rist, R. Grosset, Revue Tuberc. Pneumol., 1963, 27, 217-272.

- S. G. Franzblau, R. S. Witzig, J. C. McLaughlin, P. Torres, G. Madico, A. Hernandez, M. T. M. B. Degnan, V. K. Cook, R. M. Quenzer, R. H. Ferguson, J. Clin. Microbiol., 1998, 36, 362-366.

- J. D. Vanitha, C. N. Paramasivan. Diagn. Microbiol. Infect. Dis., 2004, 49, 179-182.

- R. S. Reis, I. Neves Jr., S. L. S. Lourenço, L. S. Fonseca, M. C. S. Lourenço, J. Clin. Microbiol., 2004, 42, 2247-2248.

- T. Mossmann. J. Immunol. Meth., 1983, 65, 55-63.

- J. R. Loset R. Brun, T. Wenzler, M. Kaiser, V. Yardley, 2009, DNDi and Pan-Asian Screening Network 1-74.

- S. Nwaka, A. Hudson. Nature Rev. Drug Discov., 2006, 5, 941-955.

Downloads

Published

2015-02-15

Issue

Vol. 4 No. 1 (2015)

Section

Medicinal Chemistry

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).