16240-04-3Relevant academic research and scientific papers
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
Thiazolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral activity in cell culture
Nitsche, Christoph,Schreier, Verena N.,Behnam, Mira A. M.,Kumar, Anil,Bartenschlager, Ralf,Klein, Christian D.
, p. 8389 - 8403 (2013/12/04)
The protease of dengue virus is a promising target for antiviral drug discovery. We here report a new generation of peptide-hybrid inhibitors of dengue protease that incorporate N-substituted 5-arylidenethiazolidinone heterocycles (rhodanines and thiazolidinediones) as N-terminal capping groups of the peptide moiety. The compounds were extensively characterized with respect to inhibition of various proteases, inhibition mechanisms, membrane permeability, antiviral activity, and cytotoxicity in cell culture. A sulfur/oxygen exchange in position 2 of the capping heterocycle (thiazolidinedione-capped vs rhodanine-capped peptide hybrids) has a significant effect on these properties and activities. The most promising in vitro affinities were observed for thiazolidinedione-based peptide hybrids containing hydrophobic groups with Ki values between 1.5 and 1.8 μM and competitive inhibition mechanisms. Rhodanine-capped peptide hybrids with hydrophobic substituents have, in correlation with their membrane permeability, a more pronounced antiviral activity in cell culture than the thiazolidinediones.
SYNTHESIS OF HETEROCYCLES VIA ENAMINES-X. REACTIONS OF 1-SUBSTITUTED-4,4,6-TRIMETHYL-1,4-DIHYDROPYRIMIDINE-2(3H)THIONE DERIVATIVES WITH α-HALOGENATED CARBOXYLIC ACIDS AND KETONES
Singh, Harjit,Singh, Paramjit,Deep, Kanwal
, p. 1655 - 1660 (2007/10/02)
2,4-dioxathiazolidine derivatives(7) have been obtained in synthetically useful yields by the condensations of easily available 1-substituted-4,4,6-trimethyl-1,4-dihydropyrimidine-2(3H) thione derivatives (4) and α-halogenated carboxylic acids in aqueous
