2. Academic Validation
  3. Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi

Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi

  • J Nat Prod. 2016 Feb 26;79(2):362-8. doi: 10.1021/acs.jnatprod.5b00990.
Minni Pirttimaa 1,  Abedelmajeed Nasereddin 2,  Dmitry Kopelyanskiy 2,  Marcel Kaiser 3,  Jari Yli-Kauhaluoma 4,  Kirsi-Marja Oksman-Caldentey 1,  Reto Brun 3,  Charles L Jaffe 2,  Vânia M Moreira 4,  Sami Alakurtti 1
Affiliations

Affiliations

  • 1 VTT Technical Research Centre of Finland Ltd, VTT , P.O. Box 1000, FI-02044 VTT Espoo, Finland.
  • 2 Department of Microbiology and Molecular Genetics, IMRIC, P.O. Box 12272, Hebrew University-Hadassah Medical School , 9112102 Jerusalem, Israel.
  • 3 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute , Socinstrasse 57, 4051 Basel, Switzerland.
  • 4 Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, University of Helsinki , Viikinkaari 5 E (P.O. Box 56), FI-00014, Helsinki, Finland.
PMID: 26849852 DOI: 10.1021/acs.jnatprod.5b00990
Abstract

Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

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