Inhibitory effect of the natural product betulin and its derivatives against the intracellular bacterium Chlamydia pneumoniae

Olli Salin, Sami Alakurtti, Leena Pohjala, Antti Siiskonen, Viola Maass, Matthias Maass, Jari Yli-Kauhaluoma, Pia Vuorela (Corresponding Author)

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39 Citations (Scopus)

Abstract

Chlamydia pneumoniae is a universal pathogen that has been indicated to play a part in the development of asthma, atherosclerosis and lung cancer. The complete eradication of this intracellular bacterium is in practice impossible with the antibiotics that are currently in use and studies on new antichlamydial compounds is challenging because Chlamydia research lacks the tools required for the genetic modification of this bacterium. Betulin is a natural lupane-class triterpene derived from plants with a wide variety of biological activities. This compound group thus has wide medical potentials, and in fact has been shown to be active against intracellular pathogens. For this reason, betulin and its derivatives were selected to be assayed against C. pneumoniae in the present study.

Thirty-two betulin derivatives were assayed against C. pneumoniae using an acute infection model in vitro. Five promising compounds with potential lead compound characteristics were identified. Compound 24 (betulin dioxime) gave a minimal inhibitory concentration (MIC) of 1 μM against strain CWL-029 and showed activity in nanomolar concentrations, as 50% inhibition was achieved at 290 nM. The antichlamydial effect of 24 was confirmed with a clinical isolate CV-6, showing a MIC of 2.2 μM. Previous research on betulin and its derivatives has not identified such a remarkable inhibition of Gram-negative bacterial growth. Furthermore, we also demonstrated that this antichlamydial activity was not due to PLA2 (EC 3.1.1.4) inhibition caused by the betulin derivatives.
Original languageEnglish
Pages (from-to)1141-1151
Number of pages11
JournalBiochemical Pharmacology
Volume80
Issue number8
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Keywords

  • Betulin
  • Betulinic acid
  • Chlamydia pneumoniae
  • Antimicrobial effect
  • Phospholipase A2

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    Salin, O., Alakurtti, S., Pohjala, L., Siiskonen, A., Maass, V., Maass, M., Yli-Kauhaluoma, J., & Vuorela, P. (2010). Inhibitory effect of the natural product betulin and its derivatives against the intracellular bacterium Chlamydia pneumoniae. Biochemical Pharmacology, 80(8), 1141-1151. https://doi.org/10.1016/j.bcp.2010.06.051