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Bulbispermine: A Crinine‐Type Amaryllidaceae Alkaloid Exhibiting Cytostatic Activity toward Apoptosis‐Resistant Glioma Cells
Author(s) -
Luchetti Giovanni,
Johnston Robert,
Mathieu Véronique,
Lefranc Florence,
Hayden Kathryn,
Andolfi Anna,
LamoralTheys Delphine,
Reisenauer Mary R.,
Champion Cody,
Pelly Stephen C.,
van Otterlo Willem A. L.,
Magedov Igor V.,
Kiss Robert,
Evidente Antonio,
Rogelj Snezna,
Kornienko Alexander
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100608
Subject(s) - alkaloid , amaryllidaceae , apoptosis , lycorine , glioma , amaryllidaceae alkaloids , biology , stereochemistry , cancer research , chemistry , botany , genetics
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.