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New derivatives of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities

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Abstract

New derivatives of 3-azabicyclo[3.2.2]nonanes were prepared and characterized using FT-IR spectroscopy, HRMS, and NMR spectroscopy. The new compounds were investigated in vitro for their antiplasmodial activities against the sensitive NF54 strain and the multiresistant K1 strain of Plasmodium falciparum, and for their antitrypanosomal activity against Trypanosoma brucei rhodesiense. The N-methyl-6,9-diphenyl-N-[(pyridin-4-yl)methyl]-3-azabicyclo[3.2.2]nonan-1-amine possessed high antiplasmodial in vitro activity against both strains of P. falciparum (NF54: IC50 = 0.848 nm; K1: IC50 = 2 nm). The most promising ones were further investigated in a mouse model for their in vivo activity against Plasmodium berghei.

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References

  1. Holota S, Kryshchyshyn A, Derkach H, Trufin Y, Demchuk I, Gzella A, Grellier P, Lesyk R (2019) Bioorg Chem 86:126

    Article  CAS  Google Scholar 

  2. Kennedy PGE (2006) Int J Parasitol 36:505

    Article  CAS  Google Scholar 

  3. Fersing C, Basmaciyan L, Boudot C, Pedron J, Hutter S, Cohen A, Castera-Ducros C, Primas N, Laget M, Casanova M, Bourgeade-Delmas S, Piednoel M, Sournia-Saquet A, Mbou VB, Courtioux B, Boutet-Robinet E, Since M, Milne R, Wyllie S, Fairlamb AH, Valentin A, Rathelot P, Verhaeghe P, Vanelle P, Azas N (2019) ACS Med Chem Lett 10:34

    Article  CAS  Google Scholar 

  4. Zanutto FV, McAlister E, Tangerina MMP, Fonseca-Santos B, Salles THC, Souza IMO, Brisbe A, Vilegas W, Chorilli M, d’Avila MA, Donnely RF, Foglio MA (2019) J Pharm Sci 108:1177

    Article  Google Scholar 

  5. Li Y, Wu Y (2003) Curr Med Chem 10:2197

    Article  CAS  Google Scholar 

  6. Maxmen A (2016) Nat Med 22:220

    Article  CAS  Google Scholar 

  7. Mohsin NA, Seebacher W, Faist J, Belaj F, Saf R, Kaiser M, Brun R, Weis R (2014) Monatsh Chem 145:1319

    Article  CAS  Google Scholar 

  8. Seebacher W, Wolkinger V, Faist J, Kaiser M, Brun R, Saf R, Bucar F, Gröblacher B, Brantner A, Merino V, Kalia Y, Scapozza L, Perozzo R, Weis R (2015) Bioorg Med Chem Lett 25:1390

    Article  CAS  Google Scholar 

  9. Ahmad S, Seebacher W, Faist J, Kaiser M, Brun R, Saf R, Weis R (2016) Arch Pharm Res 39:1391

    Article  CAS  Google Scholar 

  10. Mohsin NA, Seebacher W, Faist J, Hochegger P, Kaiser M, Mäser P, Saf R, Weis R (2018) Monatsh Chem 149:99

    Article  CAS  Google Scholar 

  11. Acevedo CH, Scotti L, Alves MF, de Diniz FFM, Scotti MT (2019) Lett Org Chem 16:81

    Article  CAS  Google Scholar 

  12. Seebacher W, Faist J, Belaj F, Saf R, Kaiser M, Brun R, Weis R (2015) Monatsh Chem 146:1299

    Article  CAS  Google Scholar 

  13. Mohsin NA, Seebacher W, Faist J, Hochegger P, Kaiser M, Mäser P, Belaj F, Saf R, Kretschmer N, Alajlani M, Turek I, Brantner A, Bauer R, Bucar F, Weis R (2018) Eur J Med Chem 143:97

    Article  CAS  Google Scholar 

  14. Mohsin NA, Seebacher W, Faist J, Kretschmer N, Bauer R, Saf R, Kaiser M, Mäser P, Weis R (2018) Monatsh Chem 149:801

    Article  CAS  Google Scholar 

  15. Weis R, Schweiger K, Seebacher W, Belaj F (1998) Tetrahedron 54:14015

    Article  CAS  Google Scholar 

  16. Ahmad S, Seebacher W, Wolkinger V, Presser A, Faist J, Kaiser M, Brun R, Saf R, Weis R (2015) Arch Pharm Res 38:1455

    Article  CAS  Google Scholar 

  17. Glaser R, Bernstein MA, Balan A (1991) Magn Reson Chem 29:766

    Article  Google Scholar 

  18. Mohsin NA, Seebacher W, Hochegger P, Faist J, Saf R, Kaiser M, Mäser P, Weis R (2019) Med Chem Res 28:742

    Article  CAS  Google Scholar 

  19. Peters W (1987) Chemotherapy and drug resistance in malaria, vol 5. Academic Press Inc, New York, p 147

    Google Scholar 

  20. Franke-Fayard B, Trueman H, Ramesar J, Mendoza J, Van Der Keur M, Van Der Linden R, Sinden RE, Waters AP, Janse CJ (2004) Mol Biochem Parasitol 137:23

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria

    Michael Hoffelner, Markus Petritsch, Werner Seebacher, Johanna Dolensky, Patrick Hochegger & Robert Weis

  2. Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia

    Sarfraz Ahmad

  3. Swiss Tropical and Public Health Institute and University of Basel, Basel, Switzerland

    Marcel Kaiser & Pascal Mäser

  4. Institute for Chemistry and Technology of Materials (ICTM), Graz University of Technology, Graz, Austria

    Robert Saf

Authors
  1. Michael Hoffelner
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  2. Markus Petritsch
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  3. Sarfraz Ahmad
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  4. Werner Seebacher
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  5. Johanna Dolensky
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  6. Patrick Hochegger
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  7. Marcel Kaiser
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  8. Pascal Mäser
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  9. Robert Saf
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  10. Robert Weis
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Corresponding author

Correspondence to Werner Seebacher.

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Ethical approval

In vivo efficacy studies in mice were conducted at the Swiss Tropical and Public Health Institute (Basel) according to the rules and regulations for the protection of animal rights (“Tierschutzverordnung”) of the Swiss “Bundesamt für Veterinärwesen”. They were approved by the veterinary office of Canton Basel-Stadt, Switzerland.

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Hoffelner, M., Petritsch, M., Ahmad, S. et al. New derivatives of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities. Monatsh Chem 150, 1959–1972 (2019). https://doi.org/10.1007/s00706-019-02509-0

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  • DOI: https://doi.org/10.1007/s00706-019-02509-0

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