Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageAmerican English
Pages (from-to)445-451
Number of pages7
JournalMedChemComm
Volume5
Issue number4
DOIs
StatePublished - Apr 2014

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