Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents

https://doi.org/10.1016/j.bmcl.2009.12.045Get rights and content

Abstract

A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC2), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis.

Graphical abstract

Synthesis of a new series of quinoline-3-carbohydrazones is presented together with the pharmacological profiles. Compounds 13e, 13i, 13k, 14a, 14c, and 14i emerged as the lead molecules with MIC ranging 0.625–5 μg/mL and did not show toxicity on Vero cells up to 62.5 μg/mL which are in comparable with the present first line anti tuberculosis drugs.

  1. Download : Download full-size image

Section snippets

Acknowledgment

Authors are thankful to Dr. Ganesh Sambhasivam, CEO, Anthem biosciences, Bangalore, India, for his invaluable support and allocation of resources for this work. They are also grateful to the Head, Chemistry Department, NITK for providing necessary laboratory facilities for the research work and valuable support.

References and notes (24)

  • R. Jain et al.

    Bioorg. Med. Chem. Lett.

    (2003)
  • B. Raju et al.

    Bioorg. Med. Chem. Lett.

    (2003)
  • A. Imramovský et al.

    Bioorg. Med. Chem.

    (2007)
  • A. Nayyar et al.

    Bioorg. Med. Chem.

    (2006)
  • D. Sriram et al.

    Bioorg. Med. Chem.

    (2006)
  • N. Sinha et al.

    Bioorg. Med. Chem. Lett.

    (2005)
  • M. Zignol et al.

    J. Infect. Dis.

    (2006)
  • D. Murugesan et al.

    Bioorg. Med. Chem.

    (2008)
  • L. Annamaria et al.

    J. Med. Chem.

    (2009)
  • J. Sarva et al.

    Chem. Med. Chem

    (2006)
  • Cited by (82)

    • Zinc complexes of hydrazone derivatives bearing 3,4-dihydroquinolin-2(1H)-one nucleus as new anti-tubercular agents

      2019, Arabian Journal of Chemistry
      Citation Excerpt :

      The transition metal complexes of quinoline hydrazone derivatives have gained increasing attention as antibacterials (Freixas and Span, 1991; Babahan et al., 2013; Banerjee et al., 2009). Recently it is reported that quinoline hydrazones and their Zn (II) complexes showed significant activity anti-tuberculosis as well as fluorescence properties (Eswaran et al., 2010; Thomas et al., 2011; Vavríkova et al., 2011; Arafa et al., 2013; Hou et al., 2012). Based on these facts, supported by literature and in continuation of our research for new antituberculosis agents (Mandewale et al., 2015a,b, 2016), we have undertaken research studies on synthesis and biological screening of some new quinoline hydrazone derivatives and their Zn (II) complexes as shown in Fig. 1.

    View all citing articles on Scopus
    View full text