Anti-leishmanial activity of betulin derivatives

Sami Alakurtti, Pia Bergström, N. Sacerdoti-Sierra, C. L. Jaffe, J. Yli-Kauhaluoma (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

24 Citations (Scopus)

Abstract

Leishmanicidal activity of 24 derivatives of naturally occurring and abundant triterpenes belonging to the lupane series, betulin, betulinic acid and betulonic acid, is described in this study. The easily modified positions of the lupane skeleton, the hydroxy groups of C-3 and C-28, as well as the carbon–carbon double bond C-20–C-29 were used as a starting point to prepare a library of triterpenoid derivatives for bioactivity studies. The compounds were evaluated against Leishmania donovani axenic amastigotes on a microplate assay at 50 μM. GI50 values of the most effective compounds were evaluated, as well as their cytotoxicity on the human macrophage cell line THP-1, and anti-leishmanial activity against L. donovani-infected THP-1 macrophages was determined. Betulonic acid was the most potent derivative, yielding a GI50 value of 14.6 μM. Promising and distinct structure–activity relationships were observed, and these compounds can be regarded as significant lead molecules for further improvement and optimization.
Original languageEnglish
Pages (from-to)123-126
Number of pages4
JournalJournal of Antibiotics
Volume63
Issue number3
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Fingerprint

Leishmania donovani
Macrophages
Triterpenes
Skeleton
Libraries
Cell Line
lupane
betulonic acid
betulin
Lead
betulinic acid

Keywords

  • Antiprotozoal agents
  • Betulin
  • Betulinic acid
  • Leishmania sp.
  • Terpenoids

Cite this

Alakurtti, S., Bergström, P., Sacerdoti-Sierra, N., Jaffe, C. L., & Yli-Kauhaluoma, J. (2010). Anti-leishmanial activity of betulin derivatives. Journal of Antibiotics, 63(3), 123-126. https://doi.org/10.1038/ja.2010.2
Alakurtti, Sami ; Bergström, Pia ; Sacerdoti-Sierra, N. ; Jaffe, C. L. ; Yli-Kauhaluoma, J. / Anti-leishmanial activity of betulin derivatives. In: Journal of Antibiotics. 2010 ; Vol. 63, No. 3. pp. 123-126.
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Alakurtti, S, Bergström, P, Sacerdoti-Sierra, N, Jaffe, CL & Yli-Kauhaluoma, J 2010, 'Anti-leishmanial activity of betulin derivatives', Journal of Antibiotics, vol. 63, no. 3, pp. 123-126. https://doi.org/10.1038/ja.2010.2

Anti-leishmanial activity of betulin derivatives. / Alakurtti, Sami; Bergström, Pia; Sacerdoti-Sierra, N.; Jaffe, C. L.; Yli-Kauhaluoma, J. (Corresponding Author).

In: Journal of Antibiotics, Vol. 63, No. 3, 2010, p. 123-126.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Jaffe, C. L.

AU - Yli-Kauhaluoma, J.

PY - 2010

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N2 - Leishmanicidal activity of 24 derivatives of naturally occurring and abundant triterpenes belonging to the lupane series, betulin, betulinic acid and betulonic acid, is described in this study. The easily modified positions of the lupane skeleton, the hydroxy groups of C-3 and C-28, as well as the carbon–carbon double bond C-20–C-29 were used as a starting point to prepare a library of triterpenoid derivatives for bioactivity studies. The compounds were evaluated against Leishmania donovani axenic amastigotes on a microplate assay at 50 μM. GI50 values of the most effective compounds were evaluated, as well as their cytotoxicity on the human macrophage cell line THP-1, and anti-leishmanial activity against L. donovani-infected THP-1 macrophages was determined. Betulonic acid was the most potent derivative, yielding a GI50 value of 14.6 μM. Promising and distinct structure–activity relationships were observed, and these compounds can be regarded as significant lead molecules for further improvement and optimization.

AB - Leishmanicidal activity of 24 derivatives of naturally occurring and abundant triterpenes belonging to the lupane series, betulin, betulinic acid and betulonic acid, is described in this study. The easily modified positions of the lupane skeleton, the hydroxy groups of C-3 and C-28, as well as the carbon–carbon double bond C-20–C-29 were used as a starting point to prepare a library of triterpenoid derivatives for bioactivity studies. The compounds were evaluated against Leishmania donovani axenic amastigotes on a microplate assay at 50 μM. GI50 values of the most effective compounds were evaluated, as well as their cytotoxicity on the human macrophage cell line THP-1, and anti-leishmanial activity against L. donovani-infected THP-1 macrophages was determined. Betulonic acid was the most potent derivative, yielding a GI50 value of 14.6 μM. Promising and distinct structure–activity relationships were observed, and these compounds can be regarded as significant lead molecules for further improvement and optimization.

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Alakurtti S, Bergström P, Sacerdoti-Sierra N, Jaffe CL, Yli-Kauhaluoma J. Anti-leishmanial activity of betulin derivatives. Journal of Antibiotics. 2010;63(3):123-126. https://doi.org/10.1038/ja.2010.2