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.
- Antiprotozoal agents
- Leishmania sp.
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