Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives

Sami Alakurtti, Tuomo Heiska, Alexandros Kiriazis, Nina Sacerdoti-Sierra, Charles L. Jaffe, Jari Yli-Kauhaluoma (Corresponding Author)

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44 Citations (Scopus)

Abstract

Betulin, a naturally occurring abundant triterpene is converted in four steps to 3,28-di-O-acetyllupa-12,18-diene. When various 4-substituted urazoles were oxidized to the corresponding urazines with iodobenzene diacetate in the presence of 3,28-di-O-acetyllupa-12,18-diene, new heterocyclic betulin derivatives were produced. These betulin derivatives were examined in a microplate assay at 50 μM for their ability to inhibit the growth of Leishmania donovani axenic amastigotes, a species that causes the fatal visceral leishmaniasis. GI50 (concentration for 50% growth inhibition) values of the most effective compounds were determined and their cytotoxicity on the human macrophage cell line THP-1 evaluated. The anti-leishmanial activity on L. donovani amastigotes growing in macrophages was also examined. The heterocycloadduct between 3,28-di-O-acetyllupa-12,18-diene and 4-methylurazine was the most effective derivative with an GI50 = 8.9 μM against L. donovani amastigotes.
Original languageEnglish
Pages (from-to)1573-1582
Number of pages10
JournalBioorganic & Medicinal Chemistry
Volume18
Issue number4
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Keywords

  • Antiprotozoal agents
  • Betulin
  • Cycloaddition
  • Leishmania sp.
  • Terpenoids

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    Alakurtti, S., Heiska, T., Kiriazis, A., Sacerdoti-Sierra, N., Jaffe, C. L., & Yli-Kauhaluoma, J. (2010). Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives. Bioorganic & Medicinal Chemistry, 18(4), 1573-1582. https://doi.org/10.1016/j.bmc.2010.01.003