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2000
Volume 21, Issue 5
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646

Abstract

Heterocyclic compounds that incorporate nitrogen and sulfur, particularly those within the thiazole family, have garnered significant attention due to their versatile synthetic properties. This interest arises from their abundance of biologically active natural products and their effectiveness as potent agrochemicals and pharmaceuticals. Among these, the thiazolidin-2,4-dione (TZD) motif plays a pivotal role in the biological functions of many important molecules. The adaptability of the TZD scaffold is further heightened by the potential for substitutions at the third and fifth positions, rendering it a widely employed moiety with diverse biological effects. TZD analogs, bearing substitutions at these positions, exhibit a wide spectrum of biological activities, with a notable emphasis on hypoglycemic effects attributed to enhanced insulin resistance through the activation of the PPAR-γ receptor. This manuscript aims to present a comprehensive review of research conducted on TZD derivatives as potential antihyperglycemic agents spanning from 2010 to the current date. The review encompasses insights into their molecular mechanisms. Thiazolidin-based chemicals have received significant attention as hypoglycemic agents and provided information on patents granted for TZD analogs.

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2025-09-28
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References

  1. NaimM.J. AlamM.J. AhmadS. NawazF. ShrivastavaN. SahuM. AlamO. Therapeutic journey of 2,4-thiazolidinediones as a versatile scaffold: An insight into structure activity relationship.Eur. J. Med. Chem.201712921825010.1016/j.ejmech.2017.02.031 28231521
    [Google Scholar]
  2. KumarH. DeepA. MarwahaR.K. Chemical synthesis, mechanism of action and anticancer potential of medicinally important thiazolidin-2,4-dione derivatives: A review.Mini Rev. Med. Chem.201919181474151610.2174/1389557519666190513093618 31092179
    [Google Scholar]
  3. BansalG. SinghS. MongaV. ThanikachalamP.V. ChawlaP. Synthesis and biological evaluation of thiazolidine-2,4-dione-pyrazole conjugates as antidiabetic, anti-inflammatory and antioxidant agents.Bioorg. Chem.20199210327110.1016/j.bioorg.2019.103271 31536952
    [Google Scholar]
  4. MahapatraM.K. KumarR. KumarM. Exploring sulfonate esters of 5-arylidene thiazolidine-2,4-diones as PTP1B inhibitors with anti-hyperglycemic activity.Med. Chem. Res.201827247648710.1007/s00044‑017‑2074‑8
    [Google Scholar]
  5. Sucheta; Tahlan, S.; Verma, P.K. Synthesis, SAR and in vitro therapeutic potentials of thiazolidine-2,4-diones.Chem. Cent. J.201812112910.1186/s13065‑018‑0496‑0 30515635
    [Google Scholar]
  6. AbdellatifK.R.A. FadalyW.A.A. KamelG.M. ElshaierY.A.M.M. El-MagdM.A. Design, synthesis, modeling studies and biological evaluation of thiazolidine derivatives containing pyrazole core as potential anti-diabetic PPAR-γ agonists and anti-inflammatory COX-2 selective inhibitors.Bioorg. Chem.201982869910.1016/j.bioorg.2018.09.034 30278282
    [Google Scholar]
  7. ElkamhawyA. KimN. HassanA.H.E. ParkJ. PaikS. YangJ.E. OhK.S. LeeB.H. LeeM.Y. ShinK.J. PaeA.N. LeeK.T. RohE.J. Thiazolidine-2,4-dione-based irreversible allosteric IKK-β kinase inhibitors: Optimization into in vivo active anti-inflammatory agents.Eur. J. Med. Chem.202018811195510.1016/j.ejmech.2019.111955 31893550
    [Google Scholar]
  8. AsatiV. BajajS. MahapatraD.K. BhartiS.K. Molecular modeling studies of some thiazolidine-2,4-dione derivatives as 15-PGDH inhibitors.Med. Chem. Res.20162519410810.1007/s00044‑015‑1442‑5
    [Google Scholar]
  9. YuI. ChoiD. LeeH.K. ChoH. Synthesis and biological evaluation of new benzylidenethiazolidine-2,4-dione derivatives as 15-hydroxyprostaglandin dehydrogenase inhibitors to control the intracellular levels of prostaglandin e2 for wound healing.Biotechnol. Bioprocess Eng.; BBE201924346447510.1007/s12257‑019‑0015‑8
    [Google Scholar]
  10. UpadhyayN. TilekarK. JänschN. SchweipertM. HessJ.D. Henze MaciasL. MrowkaP. AguileraR.J. ChoeJ. Meyer-AlmesF.J. RamaaC.S. Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation.Bioorg. Chem.202010010393410.1016/j.bioorg.2020.103934 32446120
    [Google Scholar]
  11. El-KashefH. BadrG. Abo El-MaaliN. SayedD. MelnykP. LebegueN. Abd El-KhalekR. Synthesis of a novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones as promising anti-breast cancer agents.Bioorg. Chem.20209610356910.1016/j.bioorg.2020.103569 31978680
    [Google Scholar]
  12. AbdelgawadM.A. El-AdlK. El-HddadS.S.A. ElhadyM.M. SalehN.M. KhalifaM.M. KhedrF. AlswahM. NaylA.A. GhoneimM.M. Abd El-SattarN.E.A. Design, molecular docking, synthesis, anticancer and anti-hyperglycemic assessments of thiazolidine-2,4-diones bearing sulfonylthiourea moieties as potent VEGFR-2 inhibitors and PPARγ agonists.Pharmaceuticals202215222610.3390/ph15020226 35215339
    [Google Scholar]
  13. TaghourM.S. ElkadyH. EldehnaW.M. El-DeebN.M. KenawyA.M. ElkaeedE.B. AlsfoukA.A. AlesawyM.S. MetwalyA.M. EissaI.H. Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies.J. Enzyme Inhib. Med. Chem.20223711903191710.1080/14756366.2022.2085693 35801403
    [Google Scholar]
  14. El-AdlK. SakrH. El-HddadS.S.A. El-HelbyA.G.A. NasserM. AbulkhairH.S. Design, synthesis, docking, ADMET profile, and anticancer evaluations of novel thiazolidine‐2,4‐dione derivatives as VEGFR‐2 inhibitors.Arch. Pharm.20213547200049110.1002/ardp.202000491 33788290
    [Google Scholar]
  15. SharmaR.K. YounisY. MugumbateG. NjorogeM. GutJ. RosenthalP.J. ChibaleK. Synthesis and structure–activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2.Eur. J. Med. Chem.20159050751810.1016/j.ejmech.2014.11.061 25486422
    [Google Scholar]
  16. TrotskoN. GolusJ. KazimierczakP. PanethA. PrzekoraA. GinalskaG. WujecM. Synthesis and antimycobacterial activity of thiazolidine-2,4-dione based derivatives with halogenbenzohydrazones and pyridinecarbohydrazones substituents.Eur. J. Med. Chem.202018911204510.1016/j.ejmech.2020.112045 31951961
    [Google Scholar]
  17. TrotskoN. GolusJ. KazimierczakP. PanethA. PrzekoraA. GinalskaG. WujecM. Design, synthesis and antimycobacterial activity of thiazolidine-2,4-dione-based thiosemicarbazone derivatives.Bioorg. Chem.20209710367610.1016/j.bioorg.2020.103676 32097795
    [Google Scholar]
  18. Mohammed IqbalA.K. KhanA.Y. KalashettiM.B. BelavagiN.S. GongY.D. KhaziI.A.M. Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring.Eur. J. Med. Chem.20125330831510.1016/j.ejmech.2012.04.015 22575535
    [Google Scholar]
  19. BahareR.S. GangulyS. ChoowongkomonK. SeetahaS. Synthesis, HIV-1 RT inhibitory, antibacterial, antifungal and binding mode studies of some novel N-substituted 5-benzylidine-2,4-thiazolidinediones.Daru2015231610.1186/s40199‑014‑0086‑1 25617150
    [Google Scholar]
  20. MoorthyP. EkambaramS.P. PerumalS.S. Synthesis, characterization and antimicrobial evaluation of imidazolyl thiazolidinedione derivatives.Arab. J. Chem.201912341341910.1016/j.arabjc.2014.08.010
    [Google Scholar]
  21. NastasăC.M. DumaM. PîrnăuA. VlaseL. TiperciucB. OnigaO. Development of new 5-(chromene-3-yl)methylene-2,4-thiazolidinediones as antimicrobial agents.Clujul Med.2016891122127 27004035
    [Google Scholar]
  22. SharmaS. MittalN. BanikB.K. Chemistry and therapeutic aspect of triazole: Insight into the structure-activity relationship.Curr. Pharm. Des.202329342702272010.2174/0113816128271288231023045049 37916492
    [Google Scholar]
  23. MohantyS. ReddyS.G. RamaDevi, B.; Karmakar, A.C. An assembly of structurally diverse small and simple 5-aminomethylene derivatives of 2,4-thiazolidinedione and studies of their biological activity.Med. Chem. Res.201524124037404910.1007/s00044‑015‑1447‑0
    [Google Scholar]
  24. LevshinI.B. SimonovA.Y. LavrenovS.N. PanovA.A. GrammatikovaN.E. AlexandrovA.A. GhazyE.S.M.O. SavinN.A. GorelkinP.V. ErofeevA.S. PolshakovV.I. Antifungal thiazolidines: Synthesis and biological evaluation of mycosidine congeners.Pharmaceuticals202215556310.3390/ph15050563 35631390
    [Google Scholar]
  25. KumarH. DeepA. MarwahaR.K. Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(substituted aryl/alkyl)methyl)benzylidene)thiazolidine-2,4-dione derivatives.BMC Chem.20201412510.1186/s13065‑020‑00678‑2 32266332
    [Google Scholar]
  26. MarcG. StanaA. OnigaS.D. PîrnăuA. VlaseL. OnigaO. New phenolic derivatives of thiazolidine-2,4-dione with antioxidant and antiradical properties: Synthesis, characterization, in vitro evaluation, and quantum studies.Molecules20192411206010.3390/molecules24112060 31151176
    [Google Scholar]
  27. BansalG. ThanikachalamP.V. MauryaR.K. ChawlaP. RamamurthyS. An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes.J. Adv. Res.20202316320510.1016/j.jare.2020.01.008 32154036
    [Google Scholar]
  28. KimS.G. KimD.M. WooJ.T. JangH.C. ChungC.H. KoK.S. ParkJ.H. ParkY.S. KimS.J. ChoiD.S. Efficacy and safety of lobeglitazone monotherapy in patients with type 2 diabetes mellitus over 24-weeks: a multicenter, randomized, double-blind, parallel-group, placebo controlled trial.PLoS One201494e9284310.1371/journal.pone.0092843 24736628
    [Google Scholar]
  29. KotaB. HuangT. RoufogalisB. An overview on biological mechanisms of PPARs.Pharmacol. Res.2005512859410.1016/j.phrs.2004.07.012 15629253
    [Google Scholar]
  30. Yki-JärvinenH. Thiazolidinediones.N. Engl. J. Med.2004351111106111810.1056/NEJMra041001 15356308
    [Google Scholar]
  31. WermanA. HollenbergA. SolanesG. BjørbækC. Vidal-PuigA.J. FlierJ.S. Ligand-independent activation domain in the n terminus of Peroxisome Proliferator-activated Receptor γ (PPARγ).J. Biol. Chem.199727232202302023510.1074/jbc.272.32.20230 9242701
    [Google Scholar]
  32. BergerJ. MollerD.E. The mechanisms of action of PPARs.Annu. Rev. Med.200253140943510.1146/annurev.med.53.082901.104018 11818483
    [Google Scholar]
  33. HaunerH. The mode of action of thiazolidinediones.Diabetes Metab. Res. Rev.200218S2Suppl. 2S10S1510.1002/dmrr.249 11921433
    [Google Scholar]
  34. AshwaniK. Amit, Chawla.; Sandeep, Jain.; Parvin, Kumar. Sunil, K. 3-Aryl-2-{4-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxy]-phenyl}-acrylic acid alkyl ester: synthesis and antihyperglycemicevaluation.Med. Chem. Res.20112067868610.1007/s00044‑010‑9369‑3
    [Google Scholar]
  35. Anna PratimaG. Nikalje, Design, synthesis and hypoglycemic activity of novel 2-(4-((2, 4-dioxothiazolidin-5-ylidene) methyl)-2-methoxyphenoxy)-N-substituted acetamide derivatives.Eur. J. Exp. Biol.20122413021314
    [Google Scholar]
  36. JawaleD.V. PratapU.R. RahujaN. SrivastavaA.K. ManeR.A. Synthesis and antihyperglycemic evaluation of new 2,4-thiazolidinediones having biodynamic aryl sulfonylurea moieties.Bioorg. Med. Chem. Lett.201222143643910.1016/j.bmcl.2011.10.110 22123321
    [Google Scholar]
  37. NazreenS. AlamM.S. HamidH. YarM.S. ShafiS. DhulapA.P. Alam, Pasha, M.A.Q.; Bano, S. Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-g agonists.Eur. J. Med. Chem.20148717518510.1016/j.ejmech.2014.09.010 25255433
    [Google Scholar]
  38. DatarP.A. AherS.B. Design and synthesis of novel thiazolidine-2,4-diones as hypoglycemic agents.J. Saudi Chem. Soc.201620S196S20110.1016/j.jscs.2012.10.010
    [Google Scholar]
  39. KumarH. AggarwalN. MarwahaM.G. DeepA. ChopraH. MatinM.M. RoyA. EmranT.B. MohantaY.K. AhmedR. MohantaT.K. SaravananM. MarwahaR.K. Al-HarrasiA. Thiazolidin-2,4-dione scaffold: an insight into recent advances as antimicrobial, antioxidant, and hypoglycemic agents.Molecules20222719676310.3390/molecules27196763 36235304
    [Google Scholar]
  40. NajmiA. AlamM.D. ThangavelN. TahaM.E.M. MerayaA.M. AlbrattyM. Synthesis, molecular docking, and in vivo antidiabetic evaluation of new benzylidene‐2,4‐thiazolidinediones as partial PPAR‐γ agonists.Sci. Rep.202313119869
    [Google Scholar]
  41. HamdiA. YaseenM. EwesW.A. BhatM.A. ZiedanN.I. El-ShafeyH.W. MohamedA.A.B. ElnagarM.R. HaikalA. OthmanD.I.A. ElgazarA.A. AbusabaaA.H.A. AbdelrahmanK.S. SoltanO.M. ElbadawiM.M. Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights.J. Enzyme Inhib. Med. Chem.2023381223117010.1080/14756366.2023.2231170 37470409
    [Google Scholar]
  42. TharejaS. VermaS.K. JainA.K. BharadwajT.R. Novel 5-[4-(2-biphenyl-4-yl-2-oxo-ethoxy)-benzylidene]-thiazolidine-2,4- diones, their synthesis and uses thereof.Patent WO2019/ 016826A12019
  43. CraigA.S. MillanM. Sodium Salts of 5-04-02-(n-methyl-n-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione.Patent WO02/26735A12002
  44. HalamaA. Salt of oxalic acid with 5-[4-[2-(n-methyl-n-(2-pyridyl)-amino)ethoxy]benzyl]thiazolidin-2,4-dione and a method of its preparation and its use.Patent WO2006/010345A12006
  45. MillanM.J. 5-(4-(2-(n-methyl-n-(2-pyridyl)amino)ethoxy)benzyl) thiazolidine-2,4-dione malic acid salt and use against diabetes mellitus.Patent WO03/053962A12003
  46. TakashiS. HitoshiI. Thiazolidinedione derivatives, their production and their use.Patent EP0508740A11992
  47. DolitzkyB.Z. Hydrogenation of precursors to thiazolidinedione antihyperglycemics.Patent WO03/053367A22003
  48. FangD. ZhangJ. WuL. HuS. HuX. GanY. dimethyldiguanide of the thiazolidinedione pharmaceutical, preparation method and use thereof.Patent CN101531657A2009
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