Insights into the structure and tubulin-targeted anticancer potential of N-(3-bromobenzyl) noscapine.

Abstract

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.

• Authors: Sanith Cheriyamundath, Tejashree Mahaddalkar, Praveen Kumar Reddy Nagireddy, Balasubramanian Sridhar, Srinivas Kantevari, Manu Lopus
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 71 Issue 1 Pg. 48-53 (Feb 2019) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 30465924 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Tubulin
• Tubulin Modulators
• Noscapine

Topics

• Antineoplastic Agents, Phytogenic (chemical synthesis, metabolism, pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Crystallography, X-Ray
• Female
• Humans
• Microtubules (drug effects, metabolism, pathology)
• Models, Molecular
• Molecular Structure
• Noscapine (analogs & derivatives, chemical synthesis, metabolism, pharmacology)
• Protein Binding
• Structure-Activity Relationship
• Tubulin (metabolism)
• Tubulin Modulators (chemical synthesis, metabolism, pharmacology)