3-Deazaneplanocin A and Neplanocin A analogues and their effects on apoptotic cell death

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3-Deazaneplanocin A and Neplanocin A analogues and their effects on apoptotic cell death
Title:
3-Deazaneplanocin A and Neplanocin A analogues and their effects on apoptotic cell death
Journal Title:
ChemMedChem
Keywords:
Publication Date:
15 October 2014
Citation:
Tam, E. K. W.; Nguyen, T. M.; Lim, C. Z. H.; Lee, P. L.; Li, Z. M.; Jiang, X.; Santhanakrishnan, S.; Tan, T. W.; Goh, Y. L.; Wong, S. Y.; Yang, H. Y.; Ong, E. H. Q.; Hill, J.; Yu, Q.; Chai, C. L. L., 3-Deazaneplanocin A and Neplanocin A analogues and their effects on apoptotic cell death. ChemMedChem 2015, 10 (1), 173-182.
Abstract:
3-Deazaneplanocin A (DzNep) is a potential epigenetic drug for the treatment of various cancers. DzNep has been reported to deplete histone methylations, including oncogenic EZH2 complex, giving rise to epigenetic modifications that reactivate many silenced tumor suppressors in cancer cells. Despite its promise as an anticancer drug, little is known about the structure–activity relationships of DzNep in the context of epigenetic modifications and apoptosis induction. In this study, a number of analogues of DzNep were examined for DzNep-like ability to induce synergistic apoptosis in cancer cells in combination with trichostatin A, a known histone deacetylase (HDAC) inhibitor. The structure–activity relationship data thus obtained provide valuable information on the structural requirements for biological activity. The studies identified three compounds that show similar activities to DzNep. Two of these compounds show good pharmacokinetics and safety profiles. Attempts to correlate the observed synergistic apoptotic activities with measured S-adenosylhomocysteine hydrolase (SAHH) inhibitory activities suggest that the apoptotic activity of DzNep might not be directly due to its inhibition of SAHH.
License type:
PublisherCopyrights
Funding Info:
This work was funded by the Agency for Science Technology and Research (A*STAR) (CCOG01-001-2008 and ETPL/10-FS0002).
Description:
This is the peer reviewed version of the following article: Tam, E. K. W.; Nguyen, T. M.; Lim, C. Z. H.; Lee, P. L.; Li, Z. M.; Jiang, X.; Santhanakrishnan, S.; Tan, T. W.; Goh, Y. L.; Wong, S. Y.; Yang, H. Y.; Ong, E. H. Q.; Hill, J.; Yu, Q.; Chai, C. L. L., 3-Deazaneplanocin A and Neplanocin A analogues and their effects on apoptotic cell death. ChemMedChem 2015, 10 (1), 173-182, which has been published in final form at https://dx.doi.org/10.1002/cmdc.201402315. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
ISSN:
1860-7179
1860-7187
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