Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.bmcl.2013.09.014
Title: Restraining the flexibility of the central linker in terameprocol results in constrained analogs with improved growth inhibitory activity
Authors: Ho, S.S.H.
Go, M.L. 
Keywords: Constrained analogs
Growth inhibitory activity
Structure-activity relationship
Terameprocol
Issue Date: 15-Nov-2013
Citation: Ho, S.S.H., Go, M.L. (2013-11-15). Restraining the flexibility of the central linker in terameprocol results in constrained analogs with improved growth inhibitory activity. Bioorganic and Medicinal Chemistry Letters 23 (22) : 6127-6133. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bmcl.2013.09.014
Abstract: The semi-synthetic lignan terameprocol inhibits the transcription of several inflammatory and oncogenic genes and has been evaluated for its anti-cancer properties. Here we investigated the effect of restricting the flexibility of the carbon linker connecting the terminal rings of terameprocol on its growth inhibitory activity. Conformational restriction was explored by introducing unsaturation, inserting polar entities with limited flexibility and cyclization of the connecting linker. Twenty three compounds were synthesized and evaluated on a panel of malignant human cells. The most promising compounds were those with non-polar linkers, as seen in butadiene 1a and the cyclized benzylideneindane analog 7. Both compounds were more potent than terameprocol on pancreatic BxPC-3 cells with GI50 values of 3.4 and 8.1 μM, respectively. Selected isomers of 1a (E,E) and 7 (Z) adopted low energy bent conformations that mimicked the low energy conformer of terameprocol. It is tempting to propose that conformational similarity to terameprocol may have contributed to their good activity. The scaffolds of 1a and 7 should be further investigated for their anticancer potential. © 2013 Elsevier Ltd. All rights reserved.
Source Title: Bioorganic and Medicinal Chemistry Letters
URI: http://scholarbank.nus.edu.sg/handle/10635/106306
ISSN: 0960894X
DOI: 10.1016/j.bmcl.2013.09.014
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

3
checked on Dec 12, 2018

WEB OF SCIENCETM
Citations

3
checked on Dec 5, 2018

Page view(s)

36
checked on Dec 7, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.