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2295-31-0Relevant academic research and scientific papers
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.
5-(4-Methoxybenzylidene)thiazolidine-2,4-dione-derived VEGFR-2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations
El-Adl, Khaled,Sakr, Helmy,Nasser, Mohamed,Alswah, Mohamed,Shoman, Fatma M. A.
, (2020)
A novel series of 5-(4-methoxybenzylidene)thiazolidine-2,4-dione derivatives, 5a–g and 7a–f, was designed, synthesized, and evaluated for their anticancer activity against HepG2, HCT116, and MCF-7 cells. HepG2 and HCT116 were the most sensitive cell lines to the influence of the new derivatives. In particular, compounds 7f, 7e, 7d, and 7c were found to be the most potent derivatives of all the tested compounds against the HepG2, HCT116, and MCF-7 cancer cell lines. Compound 7f (IC50 = 6.19 ± 0.5, 5.47 ± 0.3, and 7.26 ± 0.3 μM, respectively) exhibited a higher activity than sorafenib (IC50 = 9.18 ± 0.6, 8.37 ± 0.7, and 5.10 ± 0.4 μM, respectively) against HepG2 and MCF-7, cells but a lower activity against HCT116 cancer cells, respectively. Also, this compound displayed a higher activity than doxorubicin (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 μM, respectively) against HepG2 and MCF-7 cells, but nearly the same activity against HCT116 cells, respectively. All derivatives, 5a–g and 7a–f, were evaluated for their inhibitory activities against vascular endothelial growth factor receptor-2 (VEGFR-2). Among them, compound 7f was found to be the most potent derivative that inhibited VEGFR-2 at an IC50 value of 0.12 ± 0.02 μM, which is nearly the same as that of sorafenib (IC50 = 0.10 ± 0.02 μM). Compounds 7e, 7d, 7c, and 7b exhibited the highest activity, with IC50 values of 0.13 ± 0.02, 0.14 ± 0.02, 0.14 ± 0.02, and 0.18 ± 0.03 μM, respectively, which are more than the half of that of sorafenib. Furthermore, molecular docking was performed to investigate their binding mode and affinities toward the VEGFR-2 receptor. The data obtained from the docking studies highly correlated with those obtained from the biological screening.
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.
Selective cytotoxic and genotoxic activities of 5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione against NCI-H292 human lung carcinoma cells
Rodrigues, Maria do D.,Santiago, Priscila B.G.S.,Marques, Karla M.R.,Pereira, Valéria R.A.,de Castro, Maria C.A.B.,Cantalice, Jeanne C.L.L.,da Silva, Teresinha G.,Adam, M?nica L.,do Nascimento, Silene C.,de Albuquerque, Julianna F.C.,Militao, Gardenia C.G.
, p. 446 - 454 (2018)
Background: Thiazolidine-2,4-dione ring system is used as a pharmacophore to build various heterocyclic compounds aimed to interact with biological targets. In the present study, benzylidene-2,4-thiazolidinedione derivatives (compounds 2–5) were synthesized and screened against cancer cell lines and the genotoxicity and cytotoxicity of the most active compound (5) was investigated on normal and lung cancer cell line. Methods: For in vitro cytotoxic screening, the MTT assay was used for HL60 and K562 (leukemia), MCF-7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HEp-2 (cervix carcinoma) and NCI-H292 (lung carcinoma) tumor cell lines and Alamar-blue assay was used for non-tumor cells (PBMC, human peripheral blood mononuclear cells) were used. Cell morphology was visualized after Giemsa-May-Grunwald staining. DNA content, phosphatidylserine externalization and mitochondrial depolarization were measured by flow cytometry. Genotoxicity was assessed by Comet assay. Results: 5-(2-Bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione (5) presented the most potent cytotoxicity, especially against NCI-H292 lung cancer cell line, with IC50 value of 1.26 μg/mL after 72 h incubation. None of the compounds were cytotoxic to PBMC. After 48 h incubation, externalization of phosphatidylserine, mitochondrial depolarization, internucleosomal DNA fragmentation and morphological alterations consistent with apoptosis were observed in NCI-H292 cells treated with compound (5). In addition, compound (5) also induced genotoxicity in NCI-H292 cells (2.8-fold increase in damage index compared to the negative control), but not in PBMC. Conclusion: Compound 5 presented selective cytotoxic and genotoxic activity against pulmonary carcinoma (NCI-H292 cells).
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.
Synthesis of novel 2-seleno-1,8-naphthyridines derivatives
Naik, Tangali R. Ravikumar,Naik, Halehatty S. Bhojya,Naik, Halehatty R. Prakash,Raghavendra,Ramesha
, p. 1968 - 1974 (2008)
Synthesis of series of new 2-phenyl-3-(2-seleno-1,8-naphthyridin-3-yl)-2,3, 3a,6-tetrahydro-5H-pyrazolo[3,4-d][1,3]thiazol-5-ones (4a-e) has been reported. The replacement of halogen with NaHSe in the substituted 2-chloro-3-formyl-1,8- naphthyridi afforded 2-seleno-3-formyl-1,8-naphthyridins (2a - e). The reaction between (2a-e) and 1,3-thiazolidine-2,4-dione produced corresponding derivatives of substituted compounds (3a-e), which on reflux with phenyl hydrazine in DMF to generate (4a-e), with good to excellent yields. Structure of newly synthesized compounds were established based on elemental analysis, IR, 1H NMR, and mass spectral data. Copyright Taylor & Francis Group, LLC.
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.
Synthesis and characterization via molecular quantum parameters of 2H-thiazolo[3,2-a]pyrimidine-3,5,7(6H)-trione
Hamama, Wafaa S.,Ismail, Mohamed A.,Soliman, Mamdouh S.,Shaaban, Saad,Zoorob, Hanafi H.
, p. 494 - 498 (2012)
2H-Thiazolo[3,2-a]pyrimidine-3,5,7(6H)-trione (2) was synthesized and characterized via molecular quantum parameters using the PM3-semiempirical MO method. This is considered the only route not previously reported in the literature to synthesize compound 2 from 2-imino-4-thiazolidinone (1).
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.
2-ALLYLAMINOTHIAZOLIN-4-ONE IN ACYLATION REACTIONS
Levshin, I. B.,Chistyakov, V. V.,Pol'shakov, V. I.,Sheinker, Yu. N.
, p. 910 - 914 (1987)
2-Acetylallylamino-4-acetoxythiazole is obtained via treatment of 2-allylaminothiazolin-4-one with acetic anhydride for a short period of time.After extended reaction times with a mixture of acetic anhydride and acetic acid a noncondensed bicyclic derivative of thiazolidin-4-one is obtained.
