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)

Research output: Contribution to journalArticleScientificpeer-review

41 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

Fingerprint

Leishmania donovani
Macrophages
Derivatives
Triterpenes
Visceral Leishmaniasis
Cytotoxicity
Growth
Assays
Cells
Cell Line
betulin

Keywords

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

Cite this

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
Alakurtti, Sami ; Heiska, Tuomo ; Kiriazis, Alexandros ; Sacerdoti-Sierra, Nina ; Jaffe, Charles L. ; Yli-Kauhaluoma, Jari. / Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives. In: Bioorganic & Medicinal Chemistry. 2010 ; Vol. 18, No. 4. pp. 1573-1582.
@article{c3c68ee28b18467983532bf2d104fcb6,
title = "Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives",
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.",
keywords = "Antiprotozoal agents, Betulin, Cycloaddition, Leishmania sp., Terpenoids",
author = "Sami Alakurtti and Tuomo Heiska and Alexandros Kiriazis and Nina Sacerdoti-Sierra and Jaffe, {Charles L.} and Jari Yli-Kauhaluoma",
year = "2010",
doi = "10.1016/j.bmc.2010.01.003",
language = "English",
volume = "18",
pages = "1573--1582",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier",
number = "4",

}

Alakurtti, S, Heiska, T, Kiriazis, A, Sacerdoti-Sierra, N, Jaffe, CL & Yli-Kauhaluoma, J 2010, 'Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives', Bioorganic & Medicinal Chemistry, vol. 18, no. 4, pp. 1573-1582. https://doi.org/10.1016/j.bmc.2010.01.003

Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives. / Alakurtti, Sami; Heiska, Tuomo; Kiriazis, Alexandros; Sacerdoti-Sierra, Nina; Jaffe, Charles L.; Yli-Kauhaluoma, Jari (Corresponding Author).

In: Bioorganic & Medicinal Chemistry, Vol. 18, No. 4, 2010, p. 1573-1582.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives

AU - Alakurtti, Sami

AU - Heiska, Tuomo

AU - Kiriazis, Alexandros

AU - Sacerdoti-Sierra, Nina

AU - Jaffe, Charles L.

AU - Yli-Kauhaluoma, Jari

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Antiprotozoal agents

KW - Betulin

KW - Cycloaddition

KW - Leishmania sp.

KW - Terpenoids

U2 - 10.1016/j.bmc.2010.01.003

DO - 10.1016/j.bmc.2010.01.003

M3 - Article

VL - 18

SP - 1573

EP - 1582

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 4

ER -

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