Journal
PHARMACOLOGICAL REPORTS
Volume 71, Issue 1, Pages 48-53Publisher
POLISH ACAD SCIENCES INST PHARMACOLOGY
DOI: 10.1016/j.pharep.2018.09.002
Keywords
Noscapine; N-BBN; X-ray crystallography; Tubulin; Microtubules; MDA-MB-231
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Funding
- UM-DAE Centre for Excellence in Basic Sciences
- DBT-Indo-Australia biotechnology fund [BT/Indo-Aus/07/06/2013]
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Background: Noscapine is a non-narcotic, antitussive alkaloid isolated from plants of Papaveraceae family. This benzylisoquinoline alkaloid and its synthetic derivatives, called noscapinoids, are being evaluated for their anticancer potential. Methods: The structure of a novel analogue, N-(3-bromobenzyl) noscapine (N-BBN) was elucidated by X-ray crystallography. Effect of N-BBN on cancer cell proliferation and cellular microtubules were studied by sulphorhodamine B assay and immunofluorescence, respectively. Binding interactions of the alkaloid with tubulin was studied using spectrofluorimetry. Results: N-BBN, synthesized by introducing modification at site B ('N' in isoquinoline unit) and a bromo group at the 9th position of the parent compound noscapine, was found to be superior to many of the past-generation noscapinoids in inhibiting cancer cell viability and it showed a strong inhibition of the clonogenic potential of an aggressively metastatic breast tumour cell line, MDA-MB-231. The compound perturbed the tertiary structure of purified tubulin as indicated by an anilinonaphthalene sulfonic acid-binding assay. However, substantiating the common feature of noscapinoids, it did not alter microtubule polymer mass considerably. In cells, the drug-treatment showed a peculiar type of disruption of normal microtubule architecture. Conclusion: N-BBN may be considered for further investigations as a potent antiproliferative agent. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.
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