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Synthesis of new 1-benzyl tetrahydropyridin-4-ylidene piperidinium salts and their antiplasmodial and antitrypanosomal activities

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Abstract

Our last study revealed the distinct antiplasmodial and antitrypanosomal activities of 1-benzyl tetrahydropyridin-4-ylidene pyrrolidinium salts. Therefore, we prepared a series of new 1-benzyl tetrahydropyridin-4-ylidene ammonium salts with an alternative amino residue and varying substitution patterns at the benzyl group to investigate the influence of these modifications on the biological activities. All new compounds were characterized by spectroscopic methods like ultraviolet, infrared, nuclear magnetic resonance, as well as high- resolution mass spectra. They were tested for their activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense as well as for their cytotoxicity against L6 cells using microplate assays. The results show that the structure of the amino residue as well as the substitution pattern of the benzyl group influences the biological activities distinctly. Physicochemical parameters are calculated and structure–activity relationships are discussed.

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Authors and Affiliations

  1. Faculty of Pharmaceutical sciences, Government College University, Allama Iqbal Road, Faisalabad, 38000, Pakistan

    Noor-ul-Amin Mohsin

  2. Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstrasse 1, Graz, 8010, Austria

    Noor-ul-Amin Mohsin, Werner Seebacher, Patrick Hochegger, Johanna Faist & Robert Weis

  3. Institute for Chemistry and Technology of Organic Materials (ICTM), Graz University of Technology, Stremayrgasse 9, Graz, 8010, Austria

    Robert Saf

  4. Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel, 4002, Switzerland

    Marcel Kaiser & Pascal Mäser

  5. University of Basel, Petersplatz 1, Basel, 4003, Switzerland

    Marcel Kaiser & Pascal Mäser

Authors
  1. Noor-ul-Amin Mohsin
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  2. Werner Seebacher
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  3. Patrick Hochegger
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  4. Johanna Faist
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  5. Robert Saf
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  6. Marcel Kaiser
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  7. Pascal Mäser
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  8. Robert Weis
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Correspondence to Werner Seebacher.

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The authors declare that they have no conflict of interest.

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All protocols and procedures used in both in vivo studies were reviewed and approved by the local veterinary authorities of the Canton Basel-Stadt.

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Mohsin, NuA., Seebacher, W., Hochegger, P. et al. Synthesis of new 1-benzyl tetrahydropyridin-4-ylidene piperidinium salts and their antiplasmodial and antitrypanosomal activities. Med Chem Res 28, 742–753 (2019). https://doi.org/10.1007/s00044-019-02331-7

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  • DOI: https://doi.org/10.1007/s00044-019-02331-7

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