Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

R Haavikko; A Nasereddin; N Sacerdoti-Sierra; D Kopelyanskiy; Sami Alakurtti; M Tikka; C L Jaffe; J Yli-Kauhaluoma

doi:10.1039/c3md00282a

Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

R Haavikko, A Nasereddin, N Sacerdoti-Sierra, D Kopelyanskiy, Sami Alakurtti, M Tikka, C L Jaffe, J Yli-Kauhaluoma (Corresponding Author)

Research output: Contribution to journal › Article › Scientific › peer-review

39 Citations (Scopus)

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 language	English
Pages (from-to)	445-451
Number of pages	6
Journal	MedChemComm
Volume	5
Issue number	4
DOIs	https://doi.org/10.1039/c3md00282a
Publication status	Published - 2014
MoE publication type	A1 Journal article-refereed

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title = "Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes",

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",

author = "R Haavikko and A Nasereddin and N Sacerdoti-Sierra and D Kopelyanskiy and Sami Alakurtti and M Tikka and Jaffe, {C L} and J Yli-Kauhaluoma",

year = "2014",

doi = "10.1039/c3md00282a",

language = "English",

volume = "5",

pages = "445--451",

journal = "MedChemComm",

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T1 - Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

AU - Haavikko, R

AU - Nasereddin, A

AU - Sacerdoti-Sierra, N

AU - Kopelyanskiy, D

AU - Alakurtti, Sami

AU - Tikka, M

AU - Jaffe, C L

AU - Yli-Kauhaluoma, J

PY - 2014

Y1 - 2014

N2 - 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

AB - 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

U2 - 10.1039/c3md00282a

DO - 10.1039/c3md00282a

M3 - Article

VL - 5

SP - 445

EP - 451

JO - MedChemComm

JF - MedChemComm

SN - 2040-2503

IS - 4

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