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Medicinal Chemistry Research

, Volume 26, Issue 12, pp 3262–3273 | Cite as

Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids

  • Sebastian Vergara
  • Miguel Carda
  • Raül Agut
  • Lina M. Yepes
  • Iván D. Vélez
  • Sara M. Robledo
  • Wilson Cardona Galeano
Original Research
  • 99 Downloads

Abstract

The synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of 11 triclosan–hydrazone hybrids are described herein. The structure of the products was elucidated by spectral data (NMR, IR) and mass spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the major pathogenic species to Chagas disease in humans. In addition, the cytotoxic activity of the synthesized compounds was evaluated against human U-937 macrophages. Hydrazone hybrids were obtained as E-synperiplanar and E-antiperiplanar conformers. Nine of them were active against L. (V) panamensis (5a5d, 5f5j) and eight of them against T. cruzi (5a, 5c, 5d, 5f5j), with EC50 values lower than 40 µM. The compounds 5c, 5e, and 5h exhibit the best selectivity index against both L. (V) panamensis and T. cruzi, with values ranging from 5.90 to 16.55, thus showing potential as starting compounds for the eventual development of drugs against these parasites. The presence of hydroxy or methoxy groups in positions 2 and 4 of the aromatic ring of the benzylidene moiety increases both activity and cytotoxicity. There is no clear relationship between the antiprotozoal activity and the methylation pattern of the hydroxy groups, since in some cases methylation decreases the activity (5d vs. 5g) while in other cases the activity is increased (5c vs. 5f and 5i vs. 5j).

Keywords

Leishmaniasis Chagas disease Trypanosoma cruzi Antiprotozoal activity Cytotoxicity Triclosan-Hydrazone Hybrids 

Notes

Acknowledgements

The authors thank COLCIENCIAS (contract no. 0333-2013, code: 111556933423) for financial support.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sebastian Vergara
    • 1
  • Miguel Carda
    • 2
  • Raül Agut
    • 2
  • Lina M. Yepes
    • 3
  • Iván D. Vélez
    • 3
  • Sara M. Robledo
    • 3
  • Wilson Cardona Galeano
    • 1
  1. 1.Chemistry of Colombian Plants, Institute of Chemistry, Exact and Natural Sciences SchoolUniversity of Antioquia-UdeAMedellínColombia
  2. 2.Department of Inorganic and Organic ChemistryJaume I UniversityCastellónSpain
  3. 3.PECET-Medical Research Institute, School of MedicineUniversity of Antioquia-UdeAMedellínColombia

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