1010-53-3Relevant articles and documents
Design, synthesis and biological evaluation of N-substituted indole-thiazolidinedione analogues as potential pancreatic lipase inhibitors
George, Ginson,Auti, Prashant S.,Paul, Atish T.
, p. 49 - 59 (2021)
Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole-TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole-3-carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC50-6.19 and 8.96?μM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r?=.8682, p?.05). The fluorescence spectroscopic analysis further supported the strong binding affinity of these analogues with PL. A molecular dynamics study (20?ns) indicated that these analogues were stable in a dynamic environment. Thus, the present study highlighted the potential role of indole-thiazolidinedione hybrid analogues as potential PL inhibitors and further optimization might result in the development of new PL inhibitory lead candidates.
Novel N-phenyl-substituted thiazolidinediones protect neural cells against glutamate- and tBid-induced toxicity
Oppermann, Sina,Schrader, Florian C.,Els?sser, Katharina,Dolga, Amalia M.,Kraus, Anna Lena,Doti, Nunzianna,Wegscheid-Gerlach, Christof,Schlitzer, Martin,Culmsee, Carsten
, p. 273 - 289 (2014/08/18)
Mitochondrial demise is a key feature of progressive neuronal death contributing to acute and chronic neurological disorders. Recent studies identified a pivotal role for the BH3-only protein B-cell lymphoma-2 interacting domain death antagonist (Bid) for such mitochondrial damage and delayed neuronal death after oxygen-glucose deprivation, glutamate-induced excitotoxicity, or oxidative stress in vitro and after cerebral ischemia in vivo. Therefore, we developed new N-phenyl-substituted thiazolidine-2,4-dione derivatives as potent inhibitors of Bid-dependent neurotoxicity. The new compounds 6, 7, and 16 were identified as highly protective by extensive screening in a model of glutamate toxicity in immortalized mouse hippocampal neurons (HT-22 cells). These compounds significantly prevent truncated Bid-induced toxicity in the neuronal cell line, providing strong evidence that inhibition of Bid was the underlying mechanism of the observed protective effects. Furthermore, Bid-dependent hallmarks of mitochondrial dysfunction, such as loss of mitochondrial membrane potential, ATP depletion, as well as impairments in mitochondrial respiration, are significantly prevented by compounds 6, 7, and 16. Therefore, the present study identifies a class of N-phenyl thiazolidinediones as novel Bid-inhibiting neuroprotective agents that provide promising therapeutic perspectives for neurodegenerative diseases, in which Bid-mediated mitochondrial damage and associated intrinsic death pathways contribute to the underlying progressive loss of neurons. Copyright
Ionic liquid-accelerated N-arylation of 5-arylidene-2,4-thiazolidinediones with diaryliodonium salts
Yang, De-Hong,Gao, Hong-Liang,Yang, Ben-Yong,Chen, Zhen-Chu
experimental part, p. 686 - 687 (2009/09/06)
An efficient method for the synthesis of N-aryl-5-arylidene-2,4- thiazolidinediones has been developed involving the N-arylation of 5-arylidene-2,4-thiazolidinediones derivatives with diaryliodonium salts in the ionic liquid [bmim]PF6 (1-butyl-
