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Volume 24, Issue 25
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Objective

In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects.

Methods

Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus.

Results

Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5µM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site.

Conclusion

The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.

© 2024 Bentham Science Publishers
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2024-10-01
2025-06-21

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References

  1. CrooksC.M. WeilerA.M. RybarczykS.L. BlissM.I. JaegerA.S. MurphyM.E. SimmonsH.A. MejiaA. FritschM.K. HayesJ.M. EickhoffJ.C. MitzeyA.M. RazoE. BraunK.M. BrownE.A. YamamotoK. ShepherdP.M. PossellA. WeaverK. AntonyK.M. MorganT.K. NewmanC.M. DudleyD.M. Schultz-DarkenN. PetersonE. KatzelnickL.C. BalmasedaA. HarrisE. O’ConnorD.H. MohrE.L. GolosT.G. FriedrichT.C. AliotaM.T. Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques.PLoS Negl. Trop. Dis.2021157964110.1371/journal.pntd.000964134329306
     [Google Scholar]
  2. EpelboinY. TalagaS. EpelboinL. DusfourI. Zika virus: An updated review of competent or naturally infected mosquitoes.PLoS Negl. Trop. Dis.20171111593310.1371/journal.pntd.000593329145400
     [Google Scholar]
  3. LimaM.C. MendonçaL.R. RezendeA.M. CarreraR.M. Aníbal-SilvaC.E. DemersM. D’AiutoL. WoodJ. ChowdariK.V. GriffithsM. Lucena-AraujoA.R. Barral-NettoM. AzevedoE.A.N. AlvesR.W. FariasP.C.S. MarquesE.T.A. CastanhaP.M.S. DonaldC.L. KohlA. NimgaonkarV.L. FrancaR.F.O. The Transcriptional and protein profile from human infected neuroprogenitor cells is strongly correlated to zika virus microcephaly cytokines phenotype evidencing a persistent inflammation in the cns.Front. Immunol.201910192810.3389/fimmu.2019.0192831474994
     [Google Scholar]
  4. FerrarisP. YsselH. MisséD. Zika virus infection: an update.Microbes Infect.2019218-935336010.1016/j.micinf.2019.04.00531158508
     [Google Scholar]
  5. SironiM. ForniD. ClericiM. CaglianiR. Nonstructural proteins are preferential positive selection targets in zika virus and related flaviviruses.PLoS Negl. Trop. Dis.2016109497810.1371/journal.pntd.000497827588756
     [Google Scholar]
  6. LinH.H. YipB.S. HuangL.M. WuS.C. Zika virus structural biology and progress in vaccine development.Biotechnol. Adv.2018361475310.1016/j.biotechadv.2017.09.00428916391
     [Google Scholar]
  7. DuanW. SongH. WangH. ChaiY. SuC. QiJ. ShiY. GaoG.F. The crystal structure of Zika virus NS 5 reveals conserved drug targets.EMBO J.201736791993310.15252/embj.20169624128254839
     [Google Scholar]
  8. AgrelliA. de MouraR.R. CrovellaS. BrandãoL.A.C. ZIKA virus entry mechanisms in human cells.Infect. Genet. Evol.201969222910.1016/j.meegid.2019.01.01830658214
     [Google Scholar]
  9. CoutardB. BarralK. LichièreJ. SeliskoB. MartinB. AouadiW. LombardiaM.O. DebartF. VasseurJ.J. GuillemotJ.C. CanardB. DecrolyE. Zika virus methyltransferase: structure and functions for drug design perspectives.J. Virol.201791522021610.1128/JVI.02202‑1628031359
     [Google Scholar]
  10. GodoyA.S. LimaG.M.A. OliveiraK.I.Z. TorresN.U. MalufF.V. GuidoR.V.C. OlivaG. Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase.Nat. Commun.2017811476410.1038/ncomms1476428345596
     [Google Scholar]
  11. VenkataramanS. PrasadB. SelvarajanR. RNA dependent rna polymerases: insights from structure, function and evolution.Viruses20181027610.3390/v1002007629439438
     [Google Scholar]
  12. MottinM. BorbaJ.V.V.B. BragaR.C. TorresP.H.M. MartiniM.C. Proenca-ModenaJ.L. JudiceC.C. CostaF.T.M. EkinsS. PerrymanA.L. Horta AndradeC. The A–Z of Zika drug discovery.Drug Discov. Today201823111833184710.1016/j.drudis.2018.06.01429935345
     [Google Scholar]
  13. SaizJ.C. Therapeutic advances against zikv: a quick response, a long way to go. pharmaceuticals.Pharmaceuticals (Basel)201912312710.3390/ph1203012731480297
     [Google Scholar]
  14. BazM. BoivinG. Antiviral agents in development for zika virus infections.Pharmaceuticals (Basel)201912310110.3390/ph1203010131261947
     [Google Scholar]
  15. MusaddiqS. Imran ShahzadM. FirdousF. IqbalA. TanveerM. AshrafA. AslamS. KhakwaniS. Thiazolidines: potential anti-viral agents against avian influenza and infectious bronchitis viruses.Vet. Res. Forum202011441542110.30466/vrf.2018.91264.221133643596
     [Google Scholar]
  16. de OliveiraM.C.V.A. VianaD.C.F. SilvaA.A. PereiraM.C. DuarteF.S. PittaM.G.R. PittaI.R. PittaM.G.R. Synthesis of novel thiazolidinic-phthalimide derivatives evaluated as new multi-target antiepileptic agents.Bioorg. Chem.202211910554810.1016/j.bioorg.2021.10554834959174
     [Google Scholar]
  17. AnnamalaiA.S. PattnaikA. SahooB.R. MuthukrishnanE. NatarajanS.K. SteffenD. VuH.L.X. DelhonG. OsorioF.A. PetroT.M. XiangS.H. PattnaikA.K. Zika virus encoding nonglycosylated envelope protein is attenuated and defective in neuroinvasion.J. Virol.2017912313481710.1128/JVI.01348‑1728931684
     [Google Scholar]
  18. LanciottiR.S. KosoyO.L. LavenJ.J. VelezJ.O. LambertA.J. JohnsonA.J. StanfieldS.M. DuffyM.R. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007.Emerg. Infect. Dis.20081481232123910.3201/eid1408.08028718680646
     [Google Scholar]
  19. ModisY. OgataS. ClementsD. HarrisonS.C. A ligand-binding pocket in the dengue virus envelope glycoprotein.Proc. Natl. Acad. Sci. USA2003100126986699110.1073/pnas.083219310012759475
     [Google Scholar]
  20. DurrantJ.D. McCammonJ.A. BINANA: A novel algorithm for ligand-binding characterization.J. Mol. Graph. Model.201129688889310.1016/j.jmgm.2011.01.00421310640
     [Google Scholar]
  21. DeLanoW.L. The PyMOL Molecular Graphics System.San Carlos, CADeLano Scientific2002
     [Google Scholar]
  22. Gold software, version 5.2, Cambridge Crystallographic Data Centre2019http://www.ccdc.cam.ac.uk/solutions/csd-discovery/components/gold/
  23. HuangW. MoX. WuX. LuoW. ChenY. Rosiglitazone suppresses HIV-1 Tat-induced vascular inflammation via Akt signaling.Mol. Cell. Biochem.20154071-217317910.1007/s11010‑015‑2467‑226048716
     [Google Scholar]
  24. HuangJ.Y. ChouS.F. LeeJ.W. ChenH.L. ChenC.M. TaoM.H. ShihC. MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1α and PPARγ.RNA201521338540010.1261/rna.048744.11425595716
     [Google Scholar]
  25. JadavS.S. SinhaB.N. HilgenfeldR. PastorinoB. de LamballerieX. JayaprakashV. Thiazolidone derivatives as inhibitors of chikungunya virus.Eur. J. Med. Chem.20158917217810.1016/j.ejmech.2014.10.04225462237
     [Google Scholar]
  26. ManvarD. Küçükgüzelİ. ErensoyG. TatarE. DeryabaşoğullarıG. ReddyH. TaleleT.T. CevikO. Kaushik-BasuN. Discovery of conjugated thiazolidinone-thiadiazole scaffold as anti-dengue virus polymerase inhibitors.Biochem. Biophys. Res. Commun.2016469374374710.1016/j.bbrc.2015.12.04226697747
     [Google Scholar]
  27. OgorekT.J. GoldenJ.E. Advances in the development of small molecule antivirals against equine encephalitic viruses.Viruses202315241310.3390/v1502041336851628
     [Google Scholar]
  28. BenedettoA. BindaP. CostagliM. TosettiM. MorroneM.C. Predictive visuo-motor communication through neural oscillations.Curr. Biol.202131153401340810.1016/j.cub.2021.05.02634111403
     [Google Scholar]
  29. PereiraR.S. SantosF.C.P. CampanaP.R.V. CostaV.V. de PáduaR.M. SouzaD.G. TeixeiraM.M. BragaF.C. Natural products and derivatives as potential zika virus inhibitors: a comprehensive review.Viruses2023155121110.3390/v1505121137243296
     [Google Scholar]
  30. BarrowsN.J. CamposR.K. PowellS.T. PrasanthK.R. Schott-LernerG. Soto-AcostaR. Galarza-MuñozG. McGrathE.L. Urrabaz-GarzaR. GaoJ. WuP. MenonR. SaadeG. Fernandez-SalasI. RossiS.L. VasilakisN. RouthA. BradrickS.S. Garcia-BlancoM.A. A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection.Cell. Host. Microbe.201620225927010.1016/j.chom.2016.07.00427476412
     [Google Scholar]
  31. SirohiD. KuhnR.J. Zika virus structure, maturation, and receptors.J. Infect. Dis.201721693594410.1093/infdis/jix51529267925
     [Google Scholar]
  32. HertzogJ. Dias JuniorA.G. RigbyR.E. DonaldC.L. MayerA. SezginE. SongC. JinB. HublitzP. EggelingC. KohlA. RehwinkelJ. Infection with a brazilian isolate of zika virus generates rig-i stimulatory rna and the viral ns5 protein blocks type i ifn induction and signaling.Eur. J. Immunol.20184871120113610.1002/eji.20184748329572905
     [Google Scholar]
  33. NitscheC. SchreierV.N. BehnamM.A.M. KumarA. BartenschlagerR. KleinC.D. Thiazolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral activity in cell culture.J. Med. Chem.201356218389840310.1021/jm400828u24083834
     [Google Scholar]
  34. ShiryaevS.A. FarhyC. PintoA. HuangC.T. SimonettiN. NgonoA.E. DewingA. ShrestaS. PinkertonA.B. CieplakP. StronginA.Y. TerskikhA.V. Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists.Antiviral Res.201714321822910.1016/j.antiviral.2017.04.01528461069
     [Google Scholar]
  35. SharmaV. SharmaM. DhullD. SharmaY. KaushikS. KaushikS. Zika virus: an emerging challenge to public health worldwide.Can. J. Microbiol.2020662879810.1139/cjm‑2019‑033131682478
     [Google Scholar]
  36. LeeJ.Y. NguyenT.T.N. MyoungJ. Zika virus-encoded ns2a and ns4a strongly downregulate nf-κb promoter activity.J. Microbiol. Biotechnol.202030111651165910.4014/jmb.2011.1100333203823
     [Google Scholar]
  37. MuthurajP.G. KrishnamoorthyC. Anderson-BerryA. HansonC. NatarajanS.K. Novel therapeutic nutrients molecules that protect against zika virus infection with a special note on palmitoleate.Nutrients202215112410.3390/nu1501012436615782
     [Google Scholar]
  38. SreekanthG.P. Perspectives on the current antiviral developments towards RNA-dependent RNA polymerase (RdRp) and methyltransferase (MTase) domains of dengue virus non-structural protein 5 (DENV-NS5).Eur. J. Med. Chem.202325611541610.1016/j.ejmech.2023.11541637159959
     [Google Scholar]
  39. AroraR. LiewC.W. SohT.S. OtooD.A. SehC.C. YueK. NilarS. WangG. YokokawaF. NobleC.G. ChenY.L. ShiP.Y. LescarJ. SmithT.M. BensonT.E. LimS.P. Two Rna tunnel inhibitors bind in highly conserved sites in dengue virus ns5 polymerase: structural and functional studies.J. Virol.202094241130-2010.1128/JVI.01130‑2032907977
     [Google Scholar]
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Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity
Curr. Top. Med. Chem. 24, 2224 (2024); https://doi.org/10.2174/0115680266315388240801053401
/content/journals/ctmc/10.2174/0115680266315388240801053401
/content/journals/ctmc/10.2174/0115680266315388240801053401
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  • Article Type:     Research Article
Keyword(s): Antiviral activity; Chemical synthesis; Docking; RNA expression; Thiazolidine derivatives; Zika virus

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