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Issue 6, 2014
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Scaffold hopping of potential anti-tumor agents by WEGA: a shape-based approach

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Abstract

In this paper, we describe the first prospective application of the shape-comparison program, WEGA (weighted Gaussian algorithm), to find new scaffolds for anti-tumor agents. A series of sixteen carbazole alkaloids extracted from Clausena vestita D. D. Tao, which have anti-tumor activities at the cellular level, were used as query molecules. A compound library was screened by ranking molecules based upon their 3D shape and pharmacophore similarities to known inhibitors. The relationship between the structures and activities was also studied through comparative molecular field analysis (CoMFA). Twelve hits show comparable growth inhibition activity against HepG2 cells (a hit rate of 60%); eight of the hits have new scaffolds (in comparison with known inhibitors). These results indicate that a shape-based screening approach, such as WEGA, can be efficiently used for scaffold hopping in a lead identification process.

Graphical abstract: Scaffold hopping of potential anti-tumor agents by WEGA: a shape-based approach

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Supplementary files

Article information


Submitted
27 Dec 2013
Accepted
18 Mar 2014
First published
18 Mar 2014

Med. Chem. Commun., 2014,5, 737-741
Article type
Concise Article
Author version available

Scaffold hopping of potential anti-tumor agents by WEGA: a shape-based approach

H. Ge, Y. Wang, W. Zhao, W. Lin, X. Yan and J. Xu, Med. Chem. Commun., 2014, 5, 737
DOI: 10.1039/C3MD00397C

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