Bulbispermine: a crinine-type Amaryllidaceae alkaloid exhibiting cytostatic activity toward apoptosis-resistant glioma cells.

Abstract

The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small group of synthetic analogues. These, together with bulbispermine's natural crinine-type congeners, were evaluated in vitro against a panel of cancer cell lines with various levels of resistance to pro-apoptotic stimuli. Bulbispermine, haemanthamine, and haemanthidine showed the most potent antiproliferative activities as determined by the MTT colorimetric assay. Among the synthetic bulbispermine analogues, only the C1,C2-dicarbamate derivative exhibited notable growth inhibitory properties. All active compounds were found not to discriminate between the cancer cell lines based on the apoptosis sensitivity criterion; they displayed similar potencies in both cell types, indicating that the induction of apoptosis is not the primary mechanism responsible for antiproliferative activity in this series of compounds. It was also found that bulbispermine inhibits the proliferation of glioblastoma cells through cytostatic effects, possibly arising from rigidification of the actin cytoskeleton. These findings lead us to argue that crinine-type alkaloids are potentially useful drug leads for the treatment of apoptosis-resistant cancers and glioblastoma in particular.

• Authors: Giovanni Luchetti, Robert Johnston, Véronique Mathieu, Florence Lefranc, Kathryn Hayden, Anna Andolfi, Delphine Lamoral-Theys, Mary R Reisenauer, Cody Champion, Stephen C Pelly, Willem A L van Otterlo, Igor V Magedov, Robert Kiss, Antonio Evidente, Snezna Rogelj, Alexander Kornienko
• Journal: ChemMedChem (ChemMedChem) Vol. 7 Issue 5 Pg. 815-22 (May 2012) ISSN: 1860-7187 [Electronic] Germany
• PMID: 22389235 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Amaryllidaceae Alkaloids
• Antineoplastic Agents, Phytogenic
• bulbispermine
• crinine

Topics

• Amaryllidaceae Alkaloids (chemistry, pharmacology)
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Computer Simulation
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Humans
• Inhibitory Concentration 50
• Molecular Structure
• Plant Roots (chemistry)