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Noscapine Analogues

Noscapine is a tubulin-binding agent—originally extracted from opium—which has been used as a cough suppressant in human studies. It is currently an investigational anticancer agent in experimental animal and human tests.  The discovery of this plant-derived compound as a highly potent anticancer element makes it an invaluable target for extensive clinical investigations, where it could be exploited as a lead compound for designing new agents with improved bioavailability, physicochemical and pharmacoclinical properties, and lower toxicity.

Since the crystal structure of the complex of the noscapine-tubulin heterodimer has not yet been solved, our group has performed in silico studies on noscapine to address the issue using computational simulations. In particular, localization of noscapine bound to the tubulin heterodimer was investigated by employing molecular docking and molecular dynamics. Based on our results the binding site of noscapine was predicted to be in the intradomain region of α- and β-tubulin. Since noscapine has been known to have relatively few side effects, but also exhibited low efficacy, it is our expectation that improving the binding affinity for tubulin by derivatizing the noscapine compound will lead to more attractive candidate drugs for cancer chemotherapy.


Publications

L. Alisaraie and J.A. Tuszynski, Determination of Noscapine’s Localization and Interaction with the Tubulin-α/β Heterodimer, Chemical Biology & Drug Design, 78:535-546 (2011). doi:10.1111/j.1747-0285.2011.01189.x