Please use this identifier to cite or link to this item:
Title: Pyrrolidinediones reduce the toxicity of thiazolidinediones and modify their anti-diabetic and anti-cancer properties
Authors: Saha, S.
Chan, D.S.Z.
Lee, C.Y.
Wong, W.
New, L.S. 
Chui, W.K. 
Yap, C.W. 
Chan, E.C.Y. 
Ho, H.K. 
Keywords: Anti-cancer
Oxidative stress
Issue Date: 15-Dec-2012
Citation: Saha, S., Chan, D.S.Z., Lee, C.Y., Wong, W., New, L.S., Chui, W.K., Yap, C.W., Chan, E.C.Y., Ho, H.K. (2012-12-15). Pyrrolidinediones reduce the toxicity of thiazolidinediones and modify their anti-diabetic and anti-cancer properties. European Journal of Pharmacology 697 (1-3) : 13-23. ScholarBank@NUS Repository.
Abstract: Thiazolidinediones have been established as a drug class of significant importance in the treatment of Type II diabetes mellitus and have more recently displayed emergent potential as anti-cancer agents. However, their toxicity has hampered clinical development and usage in both therapeutic areas. Studies to date have implicated that the thiazolidinedione ring is responsible for the generation of reactive metabolites after metabolism. As an attempt to improve their safety profiles, we considered the bioisosteric replacement of the thiazolidinedione ring with a chemically conserved pyrrolidinedione heterocyclic system. Using pyrrolidinedione analogs of the thiazolidinedione drugs troglitazone (TGZ), rosiglitazone (RGZ), and pioglitazone (PGZ), we evaluated their PPARγ activities, anti-cancer properties as well as toxicological effects. Of significance, both pyrrolidinedione analogs demonstrated reduced toxicity. Pharmacologically, they also displayed diminished PPARγ binding and ap2 gene expression in a mouse pre-adipocyte cell line 3T3-L1, but enhanced anti-cancer properties based on the suppression of liver cancer cell line (Huh-7) proliferation and the expression of tumor marker, afp. Overall, this study ascertains the general contribution of the thiazolidinedione ring to their cytotoxicity and proposes the applicability of the pyrrolidinedione ring as a selective and safer choice in anti-diabetic and cancer chemotherapeutics for future drug design. © 2012 Elsevier B.V. All rights reserved.
Source Title: European Journal of Pharmacology
ISSN: 00142999
DOI: 10.1016/j.ejphar.2012.09.021
Appears in Collections:Staff Publications

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


checked on Jan 21, 2021


checked on Jan 12, 2021

Page view(s)

checked on Jan 17, 2021

Google ScholarTM



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