2295-31-0Relevant articles and documents
Design and synthesis of a new class of 2,4-thiazolidinedione based macrocycles suitable for Fe3+ sensing
Sepay, Nayim,Mallik, Sumitava,Saha, Pranab C.,Mallik, Asok K.
, p. 15270 - 15276 (2018)
A new class of three 2,4-thiazolidinedione based macrocycles (3a-c) have been synthesized and then characterized from spectral data and X-ray crystallography. The fluorescence quenching of the compounds caused by the addition of nineteen separate metal cations to their solutions in ethanol-water (3 : 1) was investigated, when it was observed that among the cations, the response to Fe3+ was distinctive. Again, among the macrocycles, 3c gave the best result.
Synthesis and biological evaluation of thiazolidinedione derivatives with high ligand efficiency to P. aeruginosa PhzS
Froes, Thamires Quadros,Chaves, Bianca Trindade,Mendes, Marina Sena,Ximenes, Rafael Matos,da Silva, Ivanildo Mangueira,da Silva, Priscila Brand?o Gomes,de Albuquerque, Julianna Ferreira Cavalcanti,Castilho, Marcelo Santos
, p. 1217 - 1229 (2021)
The thiazolidinone ring is found in compounds that have widespan biology activity and there is mechanism-based evidence that compounds bearing this moiety inhibit P. aeruginosa PhzS (PaPzhS), a key enzyme in the biosynthesis of the virulence factor named pyocyanin. Ten novel thiazolidinone derivatives were synthesised and screened against PaPhzS, using two orthogonal assays. The biological results provided by these and 28 other compounds, whose synthesis had been described, suggest that the dihydroquinazoline ring, found in the previous hit (A- Kd = 18 μM and LE = 0.20), is not required for PaPzhS inhibition, but unsubstituted nitrogen at the thiazolidinone ring is. The molecular simplification approach, pursued in this work, afforded an optimised lead compound (13- 5-(2,4-dimethoxyphenyl)thiazolidine-2,4-dione) with 10-fold improvement in affinity (Kd= 1.68 μM) and more than 100% increase in LE (0.45), which follows the same inhibition mode as the original hit compound (competitive to NADH).Executive summary PhzS is a key enzyme in the pyocyanin biosynthesis pathway in P. aeruginosa. Orthogonal assays (TSA and FITC) show that fragment-like thiazolidinedione derivatives bind to PaPhzS with one-digit micromolar affinity. Fragment-like thiazolidinedione derivatives bind to the cofactor (NADH) binding site in PaPhzS. The molecular simplification optimised the ligand efficiency and affinity of the lead compound.
Design, synthesis and molecular modeling studies of novel thiazolidine-2,4-dione derivatives as potential anti-cancer agents
Asati, Vivek,Bharti, Sanjay Kumar
, p. 406 - 417 (2018)
A series of novel thiazolidine-2,4-dione derivatives 4a-x have been designed, synthesized and evaluated for potential anti-cancer activity. The anti-cancer activity of synthesized compounds 4a-x were evaluated against selected human cancer cell line of breast (MCF-7) using sulforhodamine B (SRB) method. Among the synthesized compounds, 4x having 2-cyano phenyl group showed significant cytotoxic activity which is comparable to that of adriamycin as standard anti-cancer drug. The SAR study revealed that the substituted phenyl group on oxadiazole ring attached to thiazolidine-2,4-dione moiety showed significant growth inhibitory activity against MCF-7 cell line. The result of molecular modeling studies showed that compounds 4f, 4o and 4x having similar structural alignment as crystal ligand of protein (PDB code: 4DTK) and exhibited hydrogen bond interaction with amino acid residues LYS67, GLU171, ASP128 and ASP186 of PIM-1 kinase. The results of biological activity and docking study revealed that the presence of electron withdrawing group at 2 position of phenyl ring attached to oxadiazole of thiazolidine-2,4-dione scaffold is crucial for better anti-cancer activity.
Design, synthesis, molecular docking and anticancer evaluations of 5-benzylidenethiazolidine-2,4-dione derivatives targeting VEGFR-2 enzyme
Eissa, Ibrahim H.,El-Adl, Khaled,El-Hddad, Sanadelaslam S. A.,El-Helby, Abdel-Ghany A.,M. I. A. Shoman, Fatma,Sakr, Helmy
, (2020)
Novel series of 5-benzylidenethiazolidine-2,4-dione derivatives 4a-c-8a-f were designed, synthesized and evaluated for anticancer activity against HepG2, HCT-116 and MCF-7 cell lines. MCF-7 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 8f was found to be the most potent derivative overall the tested compounds against the three HepG2, HCT116 and MCF-7 cancer cell lines with IC50 = 11.19 ± 0.8, 8.99 ± 0.7 and 7.10 ± 0.4 μM respectively. Compound 8f exhibited lower activity than sorafenib, (IC50 = 9.18 ± 0.6, 8.37 ± 0.7 and 5.10 ± 0.4 μM respectively), against HepG2 and HCT116 but exhibited nearly the same activity against MCF-7 cancer cell lines respectively. Also, this compound displayed lower activity than doxorubicin, (IC50 = 7.94 ± 0.6, 8.07 ± 0.8 and 6.75 ± 0.4 μM respectively), against HepG2 and HCT116 but nearly the same activity against MCF-7cell lines respectively. The most active derivatives 6c,d,f,g and 8a-f were evaluated for their inhibitory activities against VEGFR-2. The elongation of the structures to have distal moieties enhanced anticancer and VEGFR-2 inhibitory activities as in compounds 8a-f. Among them, compounds 8f was found to be the most potent derivative that inhibited VEGFR-2 at IC50 value of 0.22 ± 0.02 μM, which is nearly the half as that of sorafenib IC50 value (0.10 ± 0.02 μM). Furthermore, molecular design was performed to investigate their binding mode and affinities towards VEGFR-2 receptor. The data obtained from docking studies were highly correlated with that obtained from the biological screening.
It is thiazolidine-2,4-dione and not thiohydantoins as the reaction product of monosubstituted thioureas and chloroacetylchloride
Yella, Ramesh,Singh, Raman Kumar,Majji, Ganesh,Patel, Bhisma K.
, p. 43 - 47 (2012)
The reaction products of monosubstituted phenylthioureas with chloroacetylchloride in a polyethylene glycol (PEG-400) medium and K2CO3 as base/catalyst at an elevated temperature are exclusively thiazolidine-2,4-diones and not thiohydantoins as has been reported. The core unit thiazolidine-2,4- dione is essentially derived from chloroacetylchloride and the thioamidic part of the phenylthiourea. The scope of this unprecedented transformation has been evaluated with electron-rich and electron-poor phenylthioureas.
Design, synthesis and evaluation of novel thiazolidinedione derivatives as anti-hyperglycemic and anti-hyperlipidemic agents
Shrivastava, Sushant K.,Batham, Ankit,Sinha, Saurabh K,Parida, Tanmaya K.,Garabadu, Debapriya,Choubey, Priyanka K.
, p. 2258 - 2266 (2016)
A novel series of thiazolidine-2,4-diones was designed, synthesized and investigated for anti-diabetic activity. The (2,4-dioxo-1,3-thiazolidin-5-yl)methylphenylbenzamide derivatives contain an amide linkage between the central aryl ring and the hydrophobic tail. Structures of the compounds were confirmed by spectroscopic techniques fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance and elemental (C, H, N) analysis. The synthesized compounds were evaluated for their in-vivo pharmacological activity (blood glucose and triglyceride lowering activity), where compounds thiazolidinediones-C and thiazolidinediones-E showed significant effects, comparable to the standard pioglitazone. Computational studies positively substantiated the nature and interaction of the designed compounds with peroxisome proliferator-activated receptor gamma.
PREPARATIVE SYNTHESIS METHOD FOR THIAZOLIDINE-2,4-DIONE AND ITS N-DERIVATIVES
Orlinskii, M. M.
, p. 144 - 145 (1995)
A procedure has been proposed for the synthesis of thiazolidine-2,4-dione and its N-derivatives, including bicyclic unfused thiazolidine-2,4-diones with alkylene and arylene bridges.The procedure is based on acid hydrolysis of the appropriate S-thiocarbaminylthiohydroacrylic acids with α-halocarboxylic acids.
Improved preparation of 2,4-thiazolidinedione
Meng, Ge,Gao, Yang,Zheng, Mei-Lin
, p. 312 - 313 (2011)
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Experimental and theoretical studies of a pyrazole-thiazolidin-2,4-di-one hybrid
Mushtaque, Md.,Avecilla, Fernando,Haque, Ashanul,Perwez, Ahmad,Khan, Md. Shahzad,Rizvi, M. Moshahid Alam
, p. 417 - 427 (2017)
The present work describes synthesis, characterization and biological evaluations of a hybrid compound 10 composed of two intriguing scaffolds pyrazole and thiazolidin-2,4-di-one. The title compound was obtained via multi-step reaction and characterized by a number of techniques (viz. IR, UV–Visible, 1H-NMR, 13C-NMR and MS) including X-ray crystallography. The structural and photophysical data of compound 10 were well supported by theoretical calculations performed at density functional (DFT) level. In-vitro anticancer studies on different human cancer cell lines indicated moderate to low activity of the compounds. The molecular target of the compound was predicted through in-silico studies. Finding of the studies are presented herein.
Synthesis of novel thiazolidinic-phthalimide derivatives evaluated as new multi-target antiepileptic agents
de Oliveira, Maria Cecilia V.A.,Viana, Douglas C.F.,Silva, Anderson A.,Pereira, Michelly C.,Duarte, Filipe S.,Pitta, Maira G.R.,Pitta, Ivan R.,Pitta, Marina G.R.
, (2021/12/27)
Epilepsy is a disease that affects millions of people around the globe and has a multifactorial cause. Inflammation is a process that can be involved in the development of seizures. Thus, the present study proposed the design and synthesis of new candidates for antiepileptic drugs that would also control the inflammatory process. Nine new derivatives of the substituted thiazophthalimide hybrid core were obtained with satisfactory purity ≥99% and yields between 27% and 87%. All compounds showed cell viability values greater than 90% in the culture of PBMC cells from healthy volunteers and, therefore, were not considered cytotoxic. These compounds modulated proinflammatory cytokines IFN-y and IL-17A and can mitigate inflammation. Acute toxicity studies of compound 7i in an animal model indicated that the compound has low toxicity and an LD50 greater than 2 g/kg in healthy adult rats. The same compound did not show positive results for anticonvulsant activity through the PTZ test. However, 7i demonstrates the interaction with the target GABA-A receptor in silico, indicating a possible activity as an agonist of that receptor. Thus, further studies are needed to investigate the anticonvulsant activity, in particular, using models in which the inflammatory process triggers epileptic seizures.
Design, synthesis, docking, ADMET profile, and anticancer evaluations of novel thiazolidine-2,4-dione derivatives as VEGFR-2 inhibitors
El-Adl, Khaled,Sakr, Helmy,El-Hddad, Sanadelaslam S. A.,El-Helby, Abdel-Ghany A.,Nasser, Mohamed,Abulkhair, Hamada S.
, (2021/04/05)
The anticancer activity of novel thiazolidine-2,4-diones was evaluated against HepG2, HCT-116, and MCF-7 cells. Among the tested cancer cell lines, HCT-116 was the most sensitive one to the cytotoxic effect of the new derivatives. In particular, compounds 18, 11, and 10 were found to be the most potent derivatives among all the tested compounds against the HepG2, HCT-116, and MCF-7 cancer cell lines, with IC50 values ranging from 38.76 to 53.99 μM. The most active antiproliferative derivatives (7–14 and 15–19) were subjected to further biological studies to evaluate their inhibitory potentials against VEGFR-2. The tested compounds displayed a good-to-medium inhibitory activity, with IC50 values ranging from 0.26 to 0.72 μM. Among them, compounds 18, 11, and 10 potently inhibited VEGFR-2 at IC50 values in the range of 0.26–0.29 μM, which are nearly three times that of the sorafenib IC50 value (0.10 μM). Although our derivatives showed lower activities than the reference drug, they could be useful as a template for future design, optimization, adaptation, and investigation to produce more potent and selective VEGFR-2 inhibitors with higher anticancer analogs. The ADMET profile showed that compounds 18, 11, and 10 do not violate any of Lipinski's rules and have a comparable intestinal absorptivity in humans. Also, the new derivatives could not inhibit cytochrome P3A4. Unlike sorafenib and doxorubicin, compounds 18, 11, and 10 are expected to have prolonged dosing intervals. Moreover, compounds 10 and 18 displayed a wide therapeutic index and higher selectivity against cancer cells as compared with their cytotoxicity against normal cells.
