18345-22-7Relevant academic research and scientific papers
Discovery of Mcl-1 inhibitors based on a thiazolidine-2,4-dione scaffold
Whiting, Ellis,Raje, Mithun R.,Chauhan, Jay,Wilder, Paul T.,Van Eker, Daniel,Hughes, Samuel J.,Bowen, Nathan G.,Vickers, Gregory E.A.,Fenimore, Ian C.,Fletcher, Steven
, p. 523 - 528 (2018)
Inspired by a rhodanine-based dual inhibitor of Bcl-xL and Mcl-1, a focused library of analogues was prepared wherein the rhodanine core was replaced with a less promiscuous thiazolidine-2,4-dione scaffold. Compounds were initially evaluated for their abilities to inhibit Mcl-1. The most potent compound 12b inhibited Mcl-1 with a Ki of 155 nM. Further investigation revealed comparable inhibition of Bcl-xL (Ki = 90 nM), indicating that the dual inhibitory profile of the initial rhodanine lead had been retained upon switching the heterocycle core.
Novel thiazolidinedione-hydroxamates as inhibitors of Mycobacterium tuberculosis virulence factor Zmp1
?lachtová, Veronika,?ebela, Marek,Torfs, Eveline,Oorts, Lauren,Cappoen, Davie,Berka, Karel,Bazgier, Václav,Brulíková, Lucie
, (2019/11/28)
Zinc metalloprotease 1 (Zmp1) is an extracellular enzyme, which has been found essential for the intracellular survival and pathogenesis of Mycobacterium tuberculosis. In this work, we designed and synthesized a series of novel thiazolidinedione-hydroxamates and evaluated in silico their drug-likeness behavior. Then, their inhibitory properties towards a recombinant Zmp1 from Mycobacterium tuberculosis were analyzed by MALDI-TOF MS. Nine of the tested compounds were found to inhibit the enzymatic reaction more effectively than the generic metalloprotease inhibitor phosphoramidon. Furthermore, the synthesized thiazolidinedione-hydroxamate hybrids were evaluated for their in vitro antimycobacterial activity and acute cytotoxicity using whole-cell assays. Results showed that none of the hybrids exhibited acute cytotoxicity against RAW264.7 macrophages. Whereas extracellular antimycobacterial activity was limited, RAW264.7 macrophage infection results showed that a majority of the hybrids inhibited the intracellular growth of Mycobacterium tuberculosis at a concentration of 100 and 10 μM. The thiazolidinedione-hydroxamate compound 2n was considered to be the best candidate of the evaluated library.
Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2
Sharma, Rajni Kant,Younis, Yassir,Mugumbate, Grace,Njoroge, Mathew,Gut, Jiri,Rosenthal, Philip J.,Chibale, Kelly
, p. 507 - 518 (2015/02/19)
Following a structure-based virtual screening, a series of 2,4 thiazolidinediones was synthesized in order to explore structure activity relationships for inhibition of the Plasmodium falciparum cysteine protease falcipain-2 (FP-2) and of whole cell antiparasitic activity. Most compounds exhibited low micromolar antiplasmodial activities against the P. falciparum drug resistant W2 strain. The most active compounds of the series were tested for in vitro microsomal metabolic stability and found to be susceptible to hepatic metabolism. Subsequent metabolite identification studies highlighted the metabolic hot spots. Molecular docking studies of a frontrunner inhibitor were carried out to determine the probable binding mode of this class of inhibitors in the active site of FP-2.
Site-specific chemical modification of peptide and protein by thiazolidinediones
Wang, Peng,Zhang, Shumei,Meng, Qiuyue,Liu, Ying,Shang, Luqing,Yin, Zheng
supporting information, p. 1361 - 1364 (2015/03/30)
A direct aldol reaction employing 2,4-thiazolidinediones as nucleophilic donors was performed to modify peptides and protein under mild conditions. Various functional groups could be readily introduced into protein without conformation change.
Systematic Evaluation of the Metabolism and Toxicity of Thiazolidinone and Imidazolidinone Heterocycles
Tang, Shi Qing,Lee, Yong Yang Irvin,Packiaraj, David Sheela,Ho, Han Kiat,Chai, Christina Li Lin
, p. 2019 - 2033 (2015/11/02)
The thiazolidine and imidazolidine heterocyclic scaffolds, i.e., the rhodanines, 2,4-thiazolidinediones, 2-thiohydantoins, and hydantoins have been the subject of debate on their suitability as starting points in drug discovery. This attention arose from the wide variety of biological activities exhibited by these scaffolds and their frequent occurrence as hits in screening campaigns. Studies have been conducted to evaluate their value in drug discovery in terms of their biological activity, chemical reactivity, aggregation-based promiscuity, and electronic properties. However, the metabolic profiles and toxicities have not been systematically assessed. In this study, a series of five-membered multiheterocyclic (FMMH) compounds were selected for a systematic evaluation of their metabolic profiles and toxicities on TAMH cells, a metabolically competent rodent liver cell line and HepG2 cells, a model of human hepatocytes. Our studies showed that generally the rhodanines are the most toxic, followed by the thiazolidinediones, thiohydantoins, and hydantoins. However, not all compounds within the family of heterocycles were toxic. In terms of metabolic stability, 5-substituted rhodanines and 5-benzylidene thiohydantoins were found to have short half-lives in the presence of human liver microsomes (t1/2 30 min) suggesting that the presence of the endocyclic sulfur and thiocarbonyl group or a combination of C5 benzylidene substituent and thiocarbonyl group in these heterocycles could be recognition motifs for P450 metabolism. However, the stability of these compounds could be improved by installing hydrophilic functional groups. Therefore, the toxicities and metabolic profiles of FMMH derivatives will ultimately depend on the overall chemical entity, and a blanket statement on the effect of the FMMH scaffold on toxicity or metabolic stability cannot and should not be made.
Synthesis, characterization, and biological evaluation of thiazolidine-2,4-dione derivatives
Alegaon, Shankar G.,Alagawadi, Kallanagouda R.,Pawar, Sneha M.,Vinod,Rajput, Udaysingh
, p. 987 - 994 (2014/03/21)
As a part of our continuation studies in developing new derivatives as dual antimicrobial/antitumor agents we describe the synthesis of new (Z)-2-(5-arylidene-2,4-dioxothiazolidin-3-yl) acetic acid derivatives (3a-m). The chemical structures of the compound were elucidated by FTIR, 1H NMR, 13C NMR, and elemental analysis data. The antimicrobial activity of all products was examined. All newly synthesized compounds were tested for their in vitro anticancer activity against four cancer cell lines. Among the synthesized compounds, 3a exhibited notable activity against HeLa, HT29, A549, and MCF-7 cell lines with IC50 values of 55, 40, 38, and 50 μM, respectively. In order to predict the drug likeliness of the synthesized compounds on the guidelines of Lipinski rule of five studies was carried out using Pallas software.
Structure-activity relationships and molecular modelling of new 5-arylidene-4-thiazolidinone derivatives as aldose reductase inhibitors and potential anti-inflammatory agents
Maccari, Rosanna,Vitale, Rosa Maria,Ottanà, Rosaria,Rocchiccioli, Marco,Marrazzo, Agostino,Cardile, Venera,Graziano, Adriana Carol Eleonora,Amodeo, Pietro,Mura, Umberto,Del Corso, Antonella
, p. 1 - 14 (2014/06/09)
A series of 5-(carbamoylmethoxy)benzylidene-2-oxo/thioxo-4-thiazolidinone derivatives (6-9) were synthesized as inhibitors of aldose reductase (AR), enzyme which plays a crucial role in the development of diabetes complications as well as in the inflammat
5-Arylidene-4-thiazolidinone derivatives active as antidegenerative agents on human chondrocyte cultures
Panico, Annamaria,MacCari, Rosanna,Cardile, Venera,Crascí, Lucia,Ronsisvalle, Simone,Ottanà, Rosaria
, p. 84 - 90 (2013/04/24)
5-Arylidene-2-oxo-4-thiazolidinones and 2-phenylimino analogues were evaluated for their antidegenerative activity on human chondrocyte cultures stimulated by IL-1β and for their inhibitory capability against matrix metalloproteinase- 13. Our results indicated that 5-arylidene-4-thiazolidinone derivatives 1-9 exhibit antidegenerative activity and could block multiple cartilage destruction during the osteoarthritic process. Out of the selected compounds, (5-arylidene- 2,4-dioxothiazolidin-3-yl)acetic acids 7-9 showed significant effectiveness in reducing NO release and restoring normal levels of GAGs in chondrocytes treated with IL-1β. Moreover, benzoic acids 1, 5 and 6 proved to be effective MMP-13 inhibitors and were able to restore normal levels of GAGs.
Synthesis and biological activities of some new thiazolidine derivatives containing pyrazole ring system
Nishida, Sho,Maruoka, Hiroshi,Yoshimura, Yuki,Goto, Takao,Tomita, Ryoko,Masumoto, Eiichi,Okabe, Fumi,Yamagata, Kenji,Fujioka, Toshihiro
experimental part, p. 303 - 309 (2012/06/30)
As a part of systematic investigation of synthesis and biologically active compounds of thiazolidine (TZD) derivatives containing pyrazole ring system, several new pyrazole-TZD derivatives 8a-d and 9a-d have been synthesized. Compounds 8a-d were prepared from N-substituted TZDs 6a-d and 1H-pyrazole-4-carboxaldehyde 7 by Knoevenagel-type reaction. Treatment of 8a-d with sodium hydride at room temperature caused dimerization reaction to afford the corresponding spirocompounds 9a-d. All the synthesized compounds were characterized by spectroscopic analysis. In vitro, the synthesized compounds 8a-d and 9a-d were tested for their growth inhibitory activity in A549 lung cancer, B16F10 murine melanoma, and HeLa human uterine carcinoma cells and for their differentiation of 3T3-L1 preadipocytes to adipocytes. The results showed that compound 8c possessed growth inhibitory effect of B16F10 cells (IC 50 = 27 μM) and compounds 9c,d had induction effect on the differentiation of 3T3-L1 preadipocytes. Copyright
Discovery of a novel submicromolar inhibitor of the lymphoid specific tyrosine phosphatase
Xie, Yuli,Liu, Yidong,Gong, Gangli,Rinderspacher, Alison,Deng, Shi-Xian,Smith, Deborah H.,Toebben, Udo,Tzilianos, Effie,Branden, Lars,Vidovic, Dusica,Chung, Caty,Schuerer, Stephan,Tautz, Lutz,Landry, Donald W.
, p. 2840 - 2844 (2008/12/21)
We report here a class of thiazolidine-2,4-diones and 2-thioxothiazolidin-4-ones as potent inhibitors of the lymphoid specific tyrosine phosphatase (Lyp) identified from high throughput screens. Chemical modification by incorporating the known phosphotyro
