Skip to content
2000
Volume 24, Issue 3
  • ISSN: 1871-5230
  • E-ISSN: 1875-614X

Abstract

Background

Obesity is one of the main health problems worldwide and is associated with type 2 diabetes mellitus. In this context, butenolides and sulfonamides are known for their anti-obesity effects.

Objectives

The present study aimed to synthesize a novel molecule containing the moieties hydroxybutenolide and sulfonamide [3-chloro-4-(-chlorophenylsulfonylamino)-5-hydroxyfuran-2(5)-one] (FS) and evaluate its metabolic effects in an obese mice model with metabolic syndrome.

Methods

4 groups of mice were divided into standard diet (ST), standard diet with added hydroxybutenolide (ST+FS), high-fat diet (HF), and high-fat diet with added hydroxybutenolide (HF+FS). Over 30 days, FS was administered by gavage at a dose of 70 mg/kg/day. Body weight, food consumption, glycemic tests, total serum cholesterol, high-density lipoprotein cholesterol, triacylglycerol, histological analyses, and gene expression by RT-PCR for the adipose tissue genes SIRT1, SIRT3, SIRT5, and NFKβ, were evaluated.

Results

A decrease in body weight was observed after FS administration (ST+FS: -7.81±4.39 and HF+FS: -11.77±9.59), reducing glucose and fasting blood glucose in the treated group. Adipose tissue mass (ST+FS: 0.017 ±0.011; HF+FS: 0.062±0.017), white epididymal adipose tissue volume, triglycerides, as well as the adipocyte area, were lower for the HF+FS group. SIRT1 and SIRT3 expressions were higher in groups that received hydroxybutenolide.

Conclusion

Treatment with FS 3-chloro-4-(-chlorophenylsulfonylamino)-5-hydroxyfuran-2(5)-one improved metabolic profile and increased the SIRT1 expression.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/aiaamc/10.2174/0118715230349902250203060705
2025-02-27
2025-09-26

  • From This Site

    /content/journals/aiaamc/10.2174/0118715230349902250203060705
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. World Health OrganizationObes. overweight.Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight 2021
  2. SantosA.C.C. AmaroL.B.R. Batista JorgeA.H. LelisS.F. LelisD.F. GuimarãesA.L.S. SantosS.H.S. AndradeJ.M.O. Curcumin improves metabolic response and increases expression of thermogenesis-associated markers in adipose tissue of male offspring from obese dams.Mol. Cell. Endocrinol.202356311184010.1016/j.mce.2022.111840 36592923
     [Google Scholar]
  3. HrubyA. HuF.B. The epidemiology of obesity: A big picture.PharmacoEconomics201533767368910.1007/s40273‑014‑0243‑x 25471927
     [Google Scholar]
  4. KeaverL. WebberL. DeeA. ShielyF. MarshT. BalandaK. PerryI. Application of the UK foresight obesity model in Ireland: The health and economic consequences of projected obesity trends in Ireland.PLoS One2013811e7982710.1371/journal.pone.0079827 24236162
     [Google Scholar]
  5. TsalamandrisS. AntonopoulosA.S. OikonomouE. PapamikroulisG.A. VogiatziG. PapaioannouS. DeftereosS. TousoulisD. The role of inflammation in diabetes: Current concepts and future perspectives.Eur. Cardiol.2019141505910.15420/ecr.2018.33.1 31131037
     [Google Scholar]
  6. SousaJ.N. QueirozL.R.P. de PaulaA.M.B. GuimarãesA.L.S. LescanoC.H. AguilarC.M. Pires de OliveiraI. SantosS.H.S. Gallic acid as a Sestrin (SESN2) activator and potential obesity therapeutic agent: A molecular docking study.Gene202388314768310.1016/j.gene.2023.147683 37536400
     [Google Scholar]
  7. ElluluM.S. PatimahI. Khaza’aiH. RahmatA. AbedY. Obesity and inflammation: The linking mechanism and the complications.Arch. Med. Sci.20174485186310.5114/aoms.2016.58928 28721154
     [Google Scholar]
  8. ZatteraleF. LongoM. NaderiJ. RacitiG.A. DesiderioA. MieleC. BeguinotF. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes.Front. Physiol.202010160710.3389/fphys.2019.01607 32063863
     [Google Scholar]
  9. DingY. XuX. Anti-inflammatory effect of exercise training through reducing inflammasome activation-related inflammatory cytokine levels in overweight/obese populations: A systematic review and meta-analysis.Complement. Ther. Clin. Pract.20224910165610.1016/j.ctcp.2022.101656 36055106
     [Google Scholar]
  10. SilvaK.A.S. FreitasD.F. BorémL.M.A. OliveiraL.P. OliveiraJ.R. ParaísoA.F. GuimarãesA.L.S. de PaulaA.M.B. D’AngelisC.E.M. SantosS.H.S. Resveratrol attenuates non-alcoholic fatty liver disease in obese mice modulating MAF1.Rev. Bras. Farmacogn.202232578679510.1007/s43450‑022‑00309‑y
     [Google Scholar]
  11. HaigisM.C. SinclairD.A. Mammalian sirtuins: Biological insights and disease relevance.Annu. Rev. Pathol.20105125329510.1146/annurev.pathol.4.110807.092250 20078221
     [Google Scholar]
  12. TangX. ChenX.F. ChenH.Z. LiuD.P. Mitochondrial Sirtuins in cardiometabolic diseases.Clin. Sci. (Lond.)2017131162063207810.1042/CS20160685 28739840
     [Google Scholar]
  13. BarbosaL.C.A. TeixeiraR.R. PinheiroP.F. MalthaC.R.Á. DemunerA.J. Estratégias para a síntese de γ-alquilidenobutenolídeos.Quim. Nova20103351163117410.1590/S0100‑40422010000500030
     [Google Scholar]
  14. TadiparthiK. VenkateshS. Synthetic approaches toward butenolide‐containing natural products.J. Heterocycl. Chem.20225981285130710.1002/jhet.4480
     [Google Scholar]
  15. GuerreroM.D. AquinoM. BrunoI. TerencioM.C. PayaM. RiccioR. Gomez-PalomaL. Synthesis and pharmacological evaluation of a selected library of new potential anti-inflammatory agents bearing the γ-hydroxybutenolide scaffold: A new class of inhibitors of prostanoid production through the selective modulation of microsomal prostaglandin E synthase-1 expression.J. Med. Chem.20075092176218410.1021/jm0700823 17407277
     [Google Scholar]
  16. MasutaniB. TsujinoY. AnJ. YamatsuA. YamashitaY. HaradaS. PPAR-gamma activator2018
     [Google Scholar]
  17. ScozzafavaA. SupuranC.T. CartaF. Antiobesity carbonic anhydrase inhibitors: A literature and patent review.Expert Opin. Ther. Pat.201323672573510.1517/13543776.2013.790957 23607332
     [Google Scholar]
  18. SupuranC.T. Special issue: Sulfonamides.Molecules20172210164210.3390/molecules22101642
     [Google Scholar]
  19. PereiraS.R. Avaliação do efeito da 3-cloro-4-(pclorofenilsulfonilamino)-5-hidroxifuran-2(5H)-ona na esteatose hepática em camundongos obesos2022
     [Google Scholar]
  20. MoraesD.S. LelisD.F. AndradeJ.M.O. MeyerL. GuimarãesA.L.S. De PaulaA.M.B. FariasL.C. SantosS.H.S. Enalapril improves obesity associated liver injury ameliorating systemic metabolic markers by modulating Angiotensin Converting Enzymes ACE/ACE2 expression in high-fat feed mice.Prostaglandins Other Lipid Mediat.202115210650110.1016/j.prostaglandins.2020.106501 33049402
     [Google Scholar]
  21. de MouraE. Dias, M.; Reis, S.A.D.; da Conceição, L.L.; de Oliveira Sediyama, C.M.N.; Pereira, S.S.; de Oliveira, L.L.; do Carmo Gouveia Peluzio, M.; Martinez, J.A.; Milagro, F.I. Diet-induced obesity in animal models: Points to consider and influence on metabolic markers.Diabetol. Metab. Syndr.20211313210.1186/s13098‑021‑00647‑2 33736684
     [Google Scholar]
  22. GuimarãesV.H.D. LelisD. de F. OliveiraL.P. BorémL.M.A. GuimarãesF.A.D. FariasL.C. de PaulaA.M.B. GuimarãesA.L.S. SantosS.H.S. Comparative study of dietary fat: Lard and sugar as a better obesity and metabolic syndrome mice model.Arch. Physiol. Biochem.2020111 33176505
     [Google Scholar]
  23. LipinskiC.A. Drug-like properties and the causes of poor solubility and poor permeability.J. Pharmacol. Toxicol. Methods200044123524910.1016/S1056‑8719(00)00107‑6 11274893
     [Google Scholar]
  24. ZhangL. YanZ. WangY. SongC. MiaoG. Design, synthesis, and biological application of novel photoaffinity probes of dihydropyridine derivatives, BAY R3401.Molecules20192413239410.3390/molecules24132394 31261804
     [Google Scholar]
  25. KurukulasuriyaR. LinkJ. MadarD. PeiZ. RichardsS. RohdeJ. SouersA. SzczepankiewiczB. Potential drug targets and progress towards pharmacologic inhibition of hepatic glucose production.Curr. Med. Chem.200310212315310.2174/0929867033368556 12570714
     [Google Scholar]
  26. TabeiY. MurotomiK. UmenoA. HorieM. TsujinoY. MasutaniB. YoshidaY. NakajimaY. Antioxidant properties of 5-hydroxy-4-phenyl-butenolide via activation of Nrf2/ARE signaling pathway.Food Chem. Toxicol.2017107Pt A12913710.1016/j.fct.2017.06.03928655653
     [Google Scholar]
  27. TsujinoY. A new agonist for peroxisome proliferation-activated receptor γ (PPARγ), fraglide-1 from Zhenjiang fragrant vinegar: Screening and characterization based on cell culture experiments.J. Oleo Sci.201766661562210.5650/jos.ess16253 28515383
     [Google Scholar]
  28. YatmazA.H. KinoshitaT. MiyazatoA. TakagiM. TsujinoY. BeppuF. GotohN. Quantification of gfragilide-1, a new functional ingrediente in vinegaras.Y. J. Oleo Sci.201766121381138610.5650/jos.ess17147 29129902
     [Google Scholar]
  29. MendesK.L. LelisD.F. de FreitasD.F. da SilveiraL.H. de PaulaA.M.B. GuimarãesA.L.S. OliveiraJ.R. AndradeM.C. NobreS.A.M. SantosS.H.S. Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.Mol. Biol. Rep.20214821725173410.1007/s11033‑021‑06190‑7 33586053
     [Google Scholar]
  30. ChungS. YaoH. CaitoS. HwangJ. ArunachalamG. RahmanI. Regulation of SIRT1 in cellular functions: Role of polyphenols.Arch. Biochem. Biophys.20105011799010.1016/j.abb.2010.05.003 20450879
     [Google Scholar]
  31. TimmersS. KoningsE. BiletL. HoutkooperR.H. van de WeijerT. GoossensG.H. HoeksJ. van der KriekenS. RyuD. KerstenS. Moonen-KornipsE. HesselinkM.K.C. KunzI. Schrauwen-HinderlingV.B. BlaakE.E. AuwerxJ. SchrauwenP. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans.Cell Metab.201114561262210.1016/j.cmet.2011.10.002 22055504
     [Google Scholar]
  32. de PinhoL. AndradeJ.M.O. ParaísoA. FilhoA.B.M. FeltenbergerJ.D. GuimarãesA.L.S. de PaulaA.M.B. CaldeiraA.P. de Carvalho BotelhoA.C. Campagnole-SantosM.J. Sousa SantosS.H. Diet composition modulates expression of sirtuins and Renin‐Angiotensin system components in adipose tissue.Obesity (Silver Spring)20132191830183510.1002/oby.20305 23408648
     [Google Scholar]
  33. JohnsonA.R. Justin MilnerJ. MakowskiL. The inflammation highway: Metabolism accelerates inflammatory traffic in obesity.Immunol. Rev.2012249121823810.1111/j.1600‑065X.2012.01151.x 22889225
     [Google Scholar]
  34. SantosS.H.S. AndradeJ.M.O. FernandesL.R. SinisterraR.D.M. SousaF.B. FeltenbergerJ.D. Alvarez-LeiteJ.I. SantosR.A.S. Oral Angiotensin-(1–7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet.Peptides201346475210.1016/j.peptides.2013.05.010 23714175
     [Google Scholar]
  35. OzyigitL.P. MoritaH. AkdisM. Innate lymphocyte cells in asthma phenotypes.Clin. Transl. Allergy2015512310.1186/s13601‑015‑0068‑5 26150907
     [Google Scholar]
  36. NieY. YangJ. ZhouL. YangZ. LiangJ. LiuY. MaX. QianZ. HongP. KalueffA.V. SongC. ZhangY. Marine fungal metabolite butyrolactone I prevents cognitive deficits by relieving inflammation and intestinal microbiota imbalance on aluminum trichloride-injured zebrafish.J. Neuroinflammation20221913910.1186/s12974‑022‑02403‑3 35130930
     [Google Scholar]
  37. TuP.C. TsengH.C. LiangY.C. HuangG.J. LuT.L. KuoT.F. KuoY.H. Phytochemical investigation of Tradescantia albiflora and anti-inflammatory butenolide derivatives.Molecules20192418333610.3390/molecules24183336 31540241
     [Google Scholar]
  38. PflugerP.T. HerranzD. Velasco-MiguelS. SerranoM. TschöpM.H. Sirt1 protects against high-fat diet-induced metabolic damage.Proc. Natl. Acad. Sci. USA2008105289793979810.1073/pnas.0802917105 18599449
     [Google Scholar]
  39. PurushothamA. SchugT.T. XuQ. SurapureddiS. GuoX. LiX. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation.Cell Metab.20099432733810.1016/j.cmet.2009.02.006 19356714
     [Google Scholar]
  40. YoshizakiT. SchenkS. ImamuraT. BabendureJ.L. SonodaN. BaeE.J. OhD.Y. LuM. MilneJ.C. WestphalC. BandyopadhyayG. OlefskyJ.M. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity.Am. J. Physiol. Endocrinol. Metab.20102983E419E42810.1152/ajpendo.00417.2009 19996381
     [Google Scholar]
  41. PicardF. KurtevM. ChungN. Topark-NgarmA. SenawongT. Machado de OliveiraR. LeidM. McBurneyM.W. GuarenteL. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ.Nature2004429699377177610.1038/nature02583 15175761
     [Google Scholar]
  42. SchugT.T. LiX. Sirtuin 1 in lipid metabolism and obesity.Ann. Med.201143319821110.3109/07853890.2010.547211 21345154
     [Google Scholar]
  43. PardoP.S. BoriekA.M. Sirtuin 1 Regulation in ageing and obesity.Mech. Ageing Dev.202018811124910.1016/j.mad.2020.111249 32320732
     [Google Scholar]
  44. XuY. YuT. MaG. ZhengL. Berberine modulates deacetylation of PPARy to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway.J. Biol. Sci.20211731733187 34421358
     [Google Scholar]
  45. SalemM.A. AborehabN.M. AbdelhafezM.M. IsmailS.H. MauriceN.W. AzzamM.A. AlseekhS. FernieA.R. SalamaM.M. EzzatS.M. Anti-Obesity effect of a tea mxture nano-fromulation on rats occcurs via the upregualtion of AMP-activated protein kinase/situin-1/gluccose transporter type 4 and peroxisome proliferator-activated receptor Gamma pathways.Metabolites202313787110.3390/metabo13070871 37512578
     [Google Scholar]
  46. BrownK. XieS. QiuX. MohrinM. ShinJ. LiuY. ZhangD. ScaddenD.T. ChenD. SIRT3 reverses aging-associated degeneration.Cell Rep.20133231932710.1016/j.celrep.2013.01.005 23375372
     [Google Scholar]
  47. Dittenhafer-ReedK.E. RichardsA.L. FanJ. SmalleganM.J. Fotuhi SiahpiraniA. KemmererZ.A. ProllaT.A. RoyS. CoonJ.J. DenuJ.M. SIRT3 mediates multi-tissue coupling for metabolic fuel switching.Cell Metab.201521463764610.1016/j.cmet.2015.03.007 25863253
     [Google Scholar]
  48. ZhangY. BaiX. ShenK. LuoL. ZhaoM. XuC. JiaY. XiaoD. LiY. GaoX. TianC. WangY. HuD. Exosomes derived from adipose mesenchymal stem cells promote diabetic chronic wound healing through SIRT3/SOD2.Cells20221116256810.3390/cells11162568 36010644
     [Google Scholar]
  49. DikalovaA.E. PandeyA. XiaoL. Mitochondrial deacetylase Sirt3 reduces vascular dysfunction and hypertension while Sirt3 depletion in essencial hypertension is linked to vascular inflammation and oxidative stress.Circ. Res.202012643945210.1161/CIRCRESAHA.119.315767 31852393
     [Google Scholar]
  50. ZhangJ. XiangH. LiuJ. ChenY. HeR.R. LiuB. Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target.Theranostics202010188315834210.7150/thno.45922 32724473
     [Google Scholar]
  51. SunW. LiuC. ChenQ. LiuN. YanY. LiuB. SIRT3: A new regulator of cardiovascular diseases.Oxid. Med. Cell. Longev.201820181729386110.1155/2018/7293861
     [Google Scholar]
/content/journals/aiaamc/10.2174/0118715230349902250203060705
Loading
Metabolic Evaluation of a Novel Hydroxyfuranone Compound: Adiposity Reduction in Obese Mice by Increasing SIRT1 Gene Expression
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) 24, 167 (2025); https://doi.org/10.2174/0118715230349902250203060705
/content/journals/aiaamc/10.2174/0118715230349902250203060705
/content/journals/aiaamc/10.2174/0118715230349902250203060705
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): adipose tissue; high-fat diet; hydroxybutenolide; metabolism; obesity; Sirtuins

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test