Issue 4, 2014
From the journal:

MedChemComm

Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes†

Raisa Haavikko,a   Abedelmajeed Nasereddin,b   Nina Sacerdoti-Sierra,b   Dmitry Kopelyanskiy,b   Sami Alakurtti,c   Mari Tikka,a   Charles L. Jaffe‡b  and  Jari Yli-Kauhaluoma*a  

* Corresponding authors

a Faculty of Pharmacy, Division of Pharmaceutical Chemistry, University of Helsinki, Viikinkaari 5 E, P. O. Box 56, FI-00014, Helsinki, Finland
E-mail: jari.yli-kauhaluoma@helsinki.fi
Tel: +358-9-191 59170

b Department of Microbiology and Molecular Genetics, IMRIC, Hebrew University-Hadassah Medical School, P. O. Box 12272, Jerusalem 91120, Israel
E-mail: cjaffe@cc.huji.ac.il
Tel: +972 26757435

c VTT Technical Research Centre of Finland, P. O. Box 1000 FI-02044 VTT, Espoo, Finland

Abstract

The synthesis of heterocyclic betulin derivatives and their activity against Leishmania donovani is reported. Betulonic acid was used as a versatile intermediate. Several different fused heterocycles were introduced at the 2,3-position of the lupane skeleton including isoxazole, pyrazine, pyridine, indole and pyrazole rings. Also the 28-position was modified. Three compounds, 5, 8 and 25, showed low micromolar activity with IC50 values of 13.2, 4.3 and 7.2 μM, respectively. Compound 8 showed the best activity and selectivity, and its activity was tested on infected macrophages using a concentration, 5 μM, where no macrophage toxicity was exhibited. Interestingly, the activity of compound 8 on axenic amastigotes and Leishmania-infected macrophages was similar.

Graphical abstract: Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

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Article information

DOI
https://doi.org/10.1039/C3MD00282A
Article type
Concise Article
Submitted
29 Sep 2013
Accepted
20 Dec 2013
First published
08 Jan 2014
This article is Open Access
Creative Commons BY-NC license

Med. Chem. Commun., 2014,5, 445-451

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Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

R. Haavikko, A. Nasereddin, N. Sacerdoti-Sierra, D. Kopelyanskiy, S. Alakurtti, M. Tikka, C. L. Jaffe and J. Yli-Kauhaluoma, Med. Chem. Commun., 2014, 5, 445 DOI: 10.1039/C3MD00282A

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