Skip to content
2000
Volume 21, Issue 18
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

This comprehensive review delves into the medicinal chemistry of amidoxime and 1,2,4-oxadiazole scaffolds. These scaffolds have been modified to address bacterial infections, malaria, inflammation, Alzheimer's disease, and cancer, yielding novel lead compounds with significant therapeutic potential. The review scrutinizes recently developed bioactive candidates, highlighting their antibacterial and anti-biofilm properties through the targeting of essential bacterial replication and virulence factors. In oncology, these derivatives exhibit promise by interacting with critical macromolecules, presenting diverse mechanisms of action. Notably, amidoxime hybrids have shown potential in inhibiting indoleamine 2,3-dioxygenase 1 (IDO1), whereas oxadiazole hybrids demonstrate anti-proliferative effects by targeting the epidermal growth factor receptor (EGFR). These hybrids also display dual inhibition of cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX), indicating significant anti-inflammatory potential. In the context of Alzheimer's disease, oxadiazoles are emerging as promising agents targeting human carbonic anhydrase (hCA) I and II enzymes. Additionally, they exhibit anti-malarial activity by targeting the Plasmodium parasite. The review further examines marketed drugs such as Ximelagatran, Upamostat, and Naldemedine, underscoring their versatile and targeted therapeutic approaches. The aim of this review is to guide medicinal chemists in synthesizing amidoximes and oxadiazoles with enhanced efficacy and reduced side effects. These scaffolds hold promising potential for future development and clinical trials.

Loading

Article metrics loading...

/content/journals/lddd/10.2174/0115701808349648241204054857
2024-12-06
2025-08-16
Loading full text...

Full text loading...

References

  1. FylaktakidouK. Hadjipavlou-LitinaD. LitinasK. VarellaE. NicolaidesD. Recent developments in the chemistry and in the biological applications of amidoximes.Curr. Pharm. Des.200814101001104710.2174/13816120878413967518473852
    [Google Scholar]
  2. BouhlelA. CurtiC. DumètreA. LagetM. CrozetM.D. AzasN. VanelleP. Synthesis and evaluation of original amidoximes as antileishmanial agents.Bioorg. Med. Chem.201018207310732010.1016/j.bmc.2010.06.09920833057
    [Google Scholar]
  3. MaračićS. GrbčićP. ShammugamS. Radić StojkovićM. PavelićK. SedićM. Kraljević PavelićS. Raić-MalićS. Amidine and amidoxime-substituted heterocycles: Synthesis, antiproliferative evaluations and DNA binding.Molecules20212622706010.3390/molecules2622706034834151
    [Google Scholar]
  4. SahyounT. ArraultA. SchneiderR. Amidoximes and oximes: Synthesis, structure, and their key role as NO donors.Molecules20192413247010.3390/molecules2413247031284390
    [Google Scholar]
  5. FörstermannU. SessaW.C. Nitric oxide synthases: regulation and function.Eur. Heart J.201233782983710.1093/eurheartj/ehr30421890489
    [Google Scholar]
  6. TousoulisD. KampoliA.M. TentolourisC. StefanadisC. The role of nitric oxide on endothelial function.Curr. Vasc. Pharmacol.201210141810.2174/15701611279882976022112350
    [Google Scholar]
  7. AldertonW.K. CooperC.E. KnowlesR.G. Nitric oxide synthases: Structure, function and inhibition.Biochem. J.2001357359361510.1042/bj357059311463332
    [Google Scholar]
  8. LundbergJ.O. GladwinM.T. WeitzbergE. Strategies to increase nitric oxide signalling in cardiovascular disease.Nat. Rev. Drug Discov.201514962364110.1038/nrd462326265312
    [Google Scholar]
  9. MohamedM.F.A. MarzoukA.A. NafadyA. El-GamalD.A. AllamR.M. Abuo-RahmaG.E.D.A. El SubbaghH.I. MoustafaA.H. Design, synthesis and molecular modeling of novel aryl carboximidamides and 3-aryl-1,2,4-oxadiazoles derived from indomethacin as potent anti-inflammatory iNOS/PGE2 inhibitors.Bioorg. Chem.202010510443910.1016/j.bioorg.2020.10443933161252
    [Google Scholar]
  10. Pimentel BarrosC.J. FreitasJ.J.R.D. OliveiraR.N.D. Freitas FilhoJ.R.D. Synthesis of amidoximes using an efficient and rapid ultrasound method.J. Chil. Chem. Soc.201156272172210.4067/S0717‑97072011000200022
    [Google Scholar]
  11. Belkhir-TalbiD. Ghemmit-DoulacheN. Terrachet-BouazizS. Makhloufi-ChebliM. RabahiA. IsmailiL. SilvaA.M.S. Transition-metal complexes of N,N′-di(4-bromophenyl)-4-hydroxycoumarin-3-carboximidamide: synthesis, characterization, biological activities, ADMET and drug-likeness analysis.Inorg. Chem. Commun.202112710850910.1016/j.inoche.2021.108509
    [Google Scholar]
  12. TassinariM. LenaA. ButovskayaE. PirotaV. NadaiM. FrecceroM. DoriaF. RichterS.N. A fragment-based approach for the development of G-quadruplex ligands: Role of the amidoxime moiety.Molecules2018238187410.3390/molecules2308187430060461
    [Google Scholar]
  13. ChylewskaA. BiedulskaM. GłębockaA. RaczyńskaE.D. MakowskiM. Drug-like properties and complete physicochemical profile of pyrazine-2-amidoxime: A combined multi-experimental and computational studies.J. Mol. Liq.201927645347010.1016/j.molliq.2018.11.147
    [Google Scholar]
  14. EttmayerP. AmidonG.L. ClementB. TestaB. Lessons learned from marketed and investigational prodrugs.J. Med. Chem.200447102393240410.1021/jm030381215115379
    [Google Scholar]
  15. MarkovA.V. Sen’kovaA.V. PopadyukI.I. SalomatinaO.V. LogashenkoE.B. KomarovaN.I. IlyinaA.A. SalakhutdinovN.F. ZenkovaM.A. Novel 3′-substituted-1′, 2′, 4′-oxadiazole derivatives of 18βH-glycyrrhetinic acid and their o-acylated amidoximes: Synthesis and evaluation of antitumor and anti-inflammatory potential in vitro and in vivo.Int. J. Mol. Sci.20202110351110.3390/ijms2110351132429154
    [Google Scholar]
  16. BiernackiK. DaśkoM. CiupakO. KubińskiK. RachonJ. DemkowiczS. Novel 1, 2, 4-oxadiazole derivatives in drug discovery.Pharmaceuticals (Basel)202013611110.3390/ph1306011132485996
    [Google Scholar]
  17. GobecM. TomašičT. MarkovičT. Mlinarič-RaščanI. DolencM.S. JakopinŽ. Antioxidant and anti-inflammatory properties of 1,2,4-oxadiazole analogs of resveratrol.Chem. Biol. Interact.201524020020710.1016/j.cbi.2015.08.01826335192
    [Google Scholar]
  18. SwaidanR. GhanemB.S. LitwillerE. PinnauI. Pure- and mixed-gas CO2/CH4 separation properties of PIM-1 and an amidoxime-functionalized PIM-1.J. Membr. Sci.20144579510210.1016/j.memsci.2014.01.055
    [Google Scholar]
  19. SimanenkoY.S. Prokop’evaT.M. BelousovaI.A. PopovA.F. KarpichevE.A. Amidoximes as Effective Acceptors of Acyl GroupTheor. Exp. Chem.200137528829510.1023/A:1013807032618
    [Google Scholar]
  20. BarbosaD.C.S. HolandaV.N. LimaE.M.A. CavalcanteM.K.A. Brelaz-de-CastroM.C.A. ChavesE.J.F. RochaG.B. SilvaC.J.O. OliveiraR.N. FigueiredoR.C.B.Q. 1,2,4-Oxadiazole Derivatives: Physicochemical Properties, Antileishmanial Potential, Docking and Molecular Dynamic Simulations of Leishmania infantum Target Proteins.Molecules20242919465410.3390/molecules2919465439407583
    [Google Scholar]
  21. JakopinZ. DolencM. Recent Advances in the Synthesis of 1,2,4- and 1,3,4-Oxadiazoles.Curr. Org. Chem.2008121085089810.2174/138527208784911860
    [Google Scholar]
  22. BoströmJ. HognerA. LlinàsA. WellnerE. PlowrightA.T. Oxadiazoles in medicinal chemistry.J. Med. Chem.20125551817183010.1021/jm201324822185670
    [Google Scholar]
  23. YanT. ChengG. YangH. 1,2,4‐Oxadiazole‐Bridged Polynitropyrazole Energetic Materials with Enhanced Thermal Stability and Low Sensitivity.ChemPlusChem201984101567157710.1002/cplu.20190045431943922
    [Google Scholar]
  24. VörösA. MucsiZ. BaánZ. TimáriG. HermeczI. MizseyP. FintaZ. An experimental and theoretical study of reaction mechanisms between nitriles and hydroxylamine.Org. Biomol. Chem.201412408036804710.1039/C4OB00854E25185027
    [Google Scholar]
  25. WarburtonW.K. The reaction of benzoyldicyandiamide [PhCO·NH·C(NH2):N·CN] with hydroxylamine hydrochloride, to give oxadiazoles.J. Chem. Soc. C1966001522152410.1039/J39660001522
    [Google Scholar]
  26. SahooA. YabanogluS. SinhaB.N. UcarG. BasuA. JayaprakashV. Towards development of selective and reversible pyrazoline based MAO-inhibitors: Synthesis, biological evaluation and docking studies.Bioorg. Med. Chem. Lett.201020113213610.1016/j.bmcl.2009.11.01519945874
    [Google Scholar]
  27. PitcherN.P. HarjaniJ.R. ZhaoY. JinJ. KnightD.R. LiL. PutsathitP. RileyT.V. CarterG.P. BaellJ.B. Development of 1, 2, 4-oxadiazole antimicrobial agents to treat enteric pathogens within the gastrointestinal tract.ACS Omega2022786737675910.1021/acsomega.1c0629435252669
    [Google Scholar]
  28. AnbazhaganM. BoykinD.W. StephensC.E. Regioselective cleavage of O-benzyl-N-arylamidoximes: synthesis of N-aryl amidines and amidoximes.Tetrahedron Lett.200243509089909210.1016/S0040‑4039(02)02289‑X
    [Google Scholar]
  29. KayukovaL.A. Synthesis of 1,2,4-oxadiazoles (a review).Pharm. Chem. J.2005391053954710.1007/s11094‑006‑0017‑7
    [Google Scholar]
  30. KhanI. IbrarA. AbbasN. Oxadiazoles as privileged motifs for promising anticancer leads: recent advances and future prospects.Arch. Pharm. (Weinheim)2014347112010.1002/ardp.20130023124265208
    [Google Scholar]
  31. BoraR.O. FarooquiM. Synthesis of substituted 1,2,4‐oxadiazoles from substituted acid chlorides and amidoximes under mild conditions.J. Heterocycl. Chem.200744364564910.1002/jhet.5570440321
    [Google Scholar]
  32. PiddockL.J.V. Understanding drug resistance will improve the treatment of bacterial infections.Nat. Rev. Microbiol.2017151163964010.1038/nrmicro.2017.12129021594
    [Google Scholar]
  33. UddinT.M. ChakrabortyA.J. KhusroA. ZidanB.M.R.M. MitraS. EmranT.B. DhamaK. RiponM.K.H. GajdácsM. SahibzadaM.U.K. HossainM.J. KoiralaN. Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects.J. Infect. Public Health202114121750176610.1016/j.jiph.2021.10.02034756812
    [Google Scholar]
  34. BaralN. MohapatraS. RaiguruB.P. MishraN.P. PandaP. NayakS. PandeyS.K. KumarP.S. SahooC.R. Microwave‐Assisted Rapid and Efficient Synthesis of New Series of Chromene‐Based 1,2,4‐Oxadiazole Derivatives and Evaluation of Antibacterial Activity with Molecular Docking Investigation.J. Heterocycl. Chem.201956255256510.1002/jhet.3430
    [Google Scholar]
  35. FrejatF.O.A. CaoY. ZhaiH. Abdel-AzizS.A. GomaaH.A.M. YoussifB.G.M. WuC. Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity.Arab. J. Chem.202215110353810.1016/j.arabjc.2021.103538
    [Google Scholar]
  36. IbrahimT.S. AlmalkiA.J. MoustafaA.H. AllamR.M. Abuo-RahmaG.E.D.A. El SubbaghH.I. MohamedM.F.A. Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study.Bioorg. Chem.202111110488510.1016/j.bioorg.2021.10488533838559
    [Google Scholar]
  37. PohW.H. RiceS.A. Recent developments in nitric oxide donors and delivery for antimicrobial and anti-biofilm applications.Molecules202227367410.3390/molecules2703067435163933
    [Google Scholar]
  38. BuomminoE. De MarinoS. SciarrettaM. PiccoloM. FestaC. D’AuriaM.V. Synergism of a Novel 1,2,4-oxadiazole-containing Derivative with Oxacillin against Methicillin-Resistant Staphylococcus aureus.Antibiotics (Basel)20211010125810.3390/antibiotics1010125834680838
    [Google Scholar]
  39. ParrinoB. CarboneD. CascioferroS. PecoraroC. GiovannettiE. DengD. Di SarnoV. MusellaS. AuriemmaG. CusimanoM.G. SchillaciD. CirrincioneG. DianaP. 1,2,4-Oxadiazole topsentin analogs as staphylococcal biofilm inhibitors targeting the bacterial transpeptidase sortase A.Eur. J. Med. Chem.202120911289210.1016/j.ejmech.2020.11289233035921
    [Google Scholar]
  40. VidyaK. Sulfonyl-Benzoxazole Based 1,2,4-Oxadiazoles: Synthesis, In Vitro Antibacterial, Antibiofilm, and In Silico ADME Studies.Russ. J. Bioorganic Chem.202248S1S101S10910.1134/S1068162023010272
    [Google Scholar]
  41. SarkarS. HornG. MoultonK. OzaA. BylerS. KokolusS. LongacreM. Cancer development, progression, and therapy: an epigenetic overview.Int. J. Mol. Sci.20131410210872111310.3390/ijms14102108724152442
    [Google Scholar]
  42. TomasettiC. LiL. VogelsteinB. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention.Science201735563311330133410.1126/science.aaf901128336671
    [Google Scholar]
  43. LevineA.J. Spontaneous and inherited TP53 genetic alterations.Oncogene202140415975598310.1038/s41388‑021‑01991‑334389799
    [Google Scholar]
  44. LianY. MengL. DingP. SangM. Epigenetic regulation of MAGE family in human cancer progression-DNA methylation, histone modification, and non-coding RNAs.Clin. Epigenetics201810111510.1186/s13148‑018‑0550‑830185218
    [Google Scholar]
  45. VineisP. AlavanjaM. BufflerP. FonthamE. FranceschiS. GaoY.T. GuptaP.C. HackshawA. MatosE. SametJ. SitasF. SmithJ. StaynerL. StraifK. ThunM.J. WichmannH.E. WuA.H. ZaridzeD. PetoR. DollR. Tobacco and cancer: recent epidemiological evidence.J. Natl. Cancer Inst.20049629910610.1093/jnci/djh01414734699
    [Google Scholar]
  46. ForayN. BourguignonM. HamadaN. Individual response to ionizing radiation.Mutat. Res. Rev. Mutat. Res.2016770Pt B36938610.1016/j.mrrev.2016.09.00127919342
    [Google Scholar]
  47. TsaiH.J. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.Taiwan. J. Obstet. Gynecol.201554211211510.1016/j.tjog.2013.11.00925951712
    [Google Scholar]
  48. MulthoffG. MollsM. RadonsJ. Chronic inflammation in cancer development.Front. Immunol.201229810.3389/fimmu.2011.0009822566887
    [Google Scholar]
  49. SharmaM. MajumdarP.K. Occupational lifestyle diseases: An emerging issue.Indian J. Occup. Environ. Med.200913310911210.4103/0019‑5278.5891220442827
    [Google Scholar]
  50. ShehadiJ.A. SciubbaD.M. SukI. SukiD. MaldaunM.V.C. McCutcheonI.E. NaderR. TheriaultR. RhinesL.D. GokaslanZ.L. Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients.Eur. Spine J.20071681179119210.1007/s00586‑007‑0357‑317406908
    [Google Scholar]
  51. YildizhanH. BarkanN.P. Karahisar TuranS. DemiralpÖ. Özel DemiralpF.D. UsluB. ŌzkanS.A. Treatment strategies in cancer from past to present. In: Drug Targeting and Stimuli Sensitive Drug Delivery Systems. GrumezescuA.M. William Andrew Publishing201813710.1016/B978‑0‑12‑813689‑8.00001‑X
    [Google Scholar]
  52. PinhoS.T.R. FreedmanH.I. NaniF. A chemotherapy model for the treatment of cancer with metastasis.Math. Comput. Model.2002367-877380310.1016/S0895‑7177(02)00227‑3
    [Google Scholar]
  53. NaranK. NundalallT. ChettyS. BarthS. Principles of Immunotherapy: Implications for Treatment Strategies in Cancer and Infectious Diseases.Front. Microbiol.20189315810.3389/fmicb.2018.0315830622524
    [Google Scholar]
  54. RossJ.S. SchenkeinD.P. PietruskoR. RolfeM. LinetteG.P. StecJ. StaglianoN.E. GinsburgG.S. SymmansW.F. PusztaiL. HortobagyiG.N. Targeted therapies for cancer 2004.Am. J. Clin. Pathol.2004122459860910.1309/5CWPU41AFR1VYM3F15487459
    [Google Scholar]
  55. SeghersP.A.L.N. WiersmaA. FestenS. StegmannM.E. SoubeyranP. RostoftS. O’HanlonS. PortieljeJ.E.A. HamakerM.E. Patient preferences for treatment outcomes in oncology with a focus on the older patient—a systematic review.Cancers (Basel)2022145114710.3390/cancers1405114735267455
    [Google Scholar]
  56. CuzickJ. ThoratM.A. AndrioleG. BrawleyO.W. BrownP.H. CuligZ. EelesR.A. FordL.G. HamdyF.C. HolmbergL. IlicD. KeyT.J. VecchiaC.L. LiljaH. MarbergerM. MeyskensF.L. MinasianL.M. ParkerC. ParnesH.L. PernerS. RittenhouseH. SchalkenJ. SchmidH.P. Schmitz-DrägerB.J. SchröderF.H. StenzlA. TombalB. WiltT.J. WolkA. Prevention and early detection of prostate cancer.Lancet Oncol.20141511e484e49210.1016/S1470‑2045(14)70211‑625281467
    [Google Scholar]
  57. MaoJ.J. PillaiG.G. AndradeC.J. LigibelJ.A. BasuP. CohenL. KhanI.A. MustianK.M. PuthiyedathR. DhimanK.S. LaoL. GhelmanR. Cáceres GuidoP. LopezG. Gallego-PerezD.F. SalicrupL.A. Integrative oncology: Addressing the global challenges of cancer prevention and treatment.CA Cancer J. Clin.202272214416410.3322/caac.2170634751943
    [Google Scholar]
  58. KeumN. GiovannucciE. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies.Nat. Rev. Gastroenterol. Hepatol.2019161271373210.1038/s41575‑019‑0189‑831455888
    [Google Scholar]
  59. KumarD. PatelG. ChaversA.K. ChangK.H. ShahK. Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents.Eur. J. Med. Chem.20114673085309210.1016/j.ejmech.2011.03.03121481985
    [Google Scholar]
  60. HuangM.R. HsuY.L. LinT.C. ChengT.J. LiL.W. TsengY.W. ChouY. LiuJ.H. PanS.H. FangJ.M. WongC.H. Structure-guided development of purine amide, hydroxamate, and amidoxime for the inhibition of non-small cell lung cancer.Eur. J. Med. Chem.201918111155110.1016/j.ejmech.2019.07.05431376567
    [Google Scholar]
  61. KumarD. PatelG. JohnsonE.O. ShahK. Synthesis and anticancer activities of novel 3,5-disubstituted-1,2,4-oxadiazoles.Bioorg. Med. Chem. Lett.200919102739274110.1016/j.bmcl.2009.03.15819376704
    [Google Scholar]
  62. AlyA.A. BräseS. HassanA.A. MohamedN.K. El-HaleemL.E.A. NiegerM. MorsyN.M. AlshammariM.B. IbrahimM.A.A. AbdelhafezE.M.N. Design, Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents.Molecules20202523556910.3390/molecules2523556933260954
    [Google Scholar]
  63. CarboneD. ParrinoB. CascioferroS. PecoraroC. GiovannettiE. Di SarnoV. MusellaS. AuriemmaG. CirrincioneG. DianaP. 1,2,4‐Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase.ChemMedChem202116353755410.1002/cmdc.20200075233141472
    [Google Scholar]
  64. GujjarappaR. SravaniS. KabiA.K. GargA. VodnalaN. TyagiU. KaldhiD. SinghV. GuptaS. MalakarC.C. An Overview on Biological Activities of Oxazole, Isoxazoles and 1,2,4-Oxadiazoles Derivatives.In: Nanostructured Biomaterials: Basic Structures and Applications. SwainB.P. Springer Singapore, Singapore202237940010.1007/978‑981‑16‑8399‑2_10
    [Google Scholar]
  65. WeeP. WangZ. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways.Cancers (Basel)2017955210.3390/cancers905005228513565
    [Google Scholar]
  66. GridelliC. RossiA. CarboneD.P. GuarizeJ. KarachaliouN. MokT. PetrellaF. SpaggiariL. RosellR. Non-small-cell lung cancer.Nat. Rev. Dis. Primers2015111500910.1038/nrdp.2015.927188576
    [Google Scholar]
  67. DoklaE.M.E. FangC.S. AbouzidK.A.M. ChenC.S. 1,2,4-Oxadiazole derivatives targeting EGFR and c-Met degradation in TKI resistant NSCLC.Eur. J. Med. Chem.201918211160710.1016/j.ejmech.2019.11160731446247
    [Google Scholar]
  68. DuQ. FengX. WangY. XuX. ZhangY. QuX. LiZ. BianJ. Discovery of phosphonamidate IDO1 inhibitors for the treatment of non-small cell lung cancer.Eur. J. Med. Chem.201918211162910.1016/j.ejmech.2019.11162931445231
    [Google Scholar]
  69. PardollD.M. The blockade of immune checkpoints in cancer immunotherapy.Nat. Rev. Cancer201212425226410.1038/nrc323922437870
    [Google Scholar]
  70. U.S. Department of Health and Human Services National Institutes of Health, N.C. Institute., Immune Checkpoint Inhibitors.2022Available from https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors
    [Google Scholar]
  71. KimJ. ChaY.N. SurhY.J. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders.Mutat. Res.20106901-2122310.1016/j.mrfmmm.2009.09.00719799917
    [Google Scholar]
  72. GalloriniM. CarradoriS. PanieriE. SovaM. SasoL. Modulation of NRF2: biological dualism in cancer, targets and possible therapeutic applications.Antioxid. Redox Signal.202310.1089/ars.2022.021337470218
    [Google Scholar]
  73. AyoupM.S. Abu-SerieM.M. Abdel-HamidH. TelebM. Beyond direct Nrf2 activation; reinvestigating 1,2,4-oxadiazole scaffold as a master key unlocking the antioxidant cellular machinery for cancer therapy.Eur. J. Med. Chem.202122011347510.1016/j.ejmech.2021.11347533901898
    [Google Scholar]
  74. DeweeseJ.E. OsheroffM.A. OsheroffN. DNA topology and topoisomerases.Biochem. Mol. Biol. Educ.200937121010.1002/bmb.2024419225573
    [Google Scholar]
  75. DehshahriA. AshrafizadehM. Ghasemipour AfsharE. PardakhtyA. MandegaryA. MohammadinejadR. SethiG. Topoisomerase inhibitors: Pharmacology and emerging nanoscale delivery systems.Pharmacol. Res.202015110455110.1016/j.phrs.2019.10455131743776
    [Google Scholar]
  76. BradburyB. PucciM. Recent advances in bacterial topoisomerase inhibitors.Curr. Opin. Pharmacol.20088557458110.1016/j.coph.2008.04.00918555745
    [Google Scholar]
  77. PilatiP. NittiD. MocellinS. Cancer resistance to type II topoisomerase inhibitors.Curr. Med. Chem.201219233900390610.2174/09298671280200247322788766
    [Google Scholar]
  78. WangW. Tse-DinhY.C. Recent advances in use of topoisomerase inhibitors in combination cancer therapy.Curr. Top. Med. Chem.201919973074010.2174/156802661966619040111335030931861
    [Google Scholar]
  79. Abdel hameid, M.K. Design, Synthesis, and Screening of 5-Aryl-3-(2-(pyrrolyl)thiophenyl)-1,2,4-oxadiazoles as Potential Antitumor Molecules on Breast Cancer MCF-7 Cell Line.Chem. Pharm. Bull. (Tokyo)201866121181119510.1248/cpb.c18‑0063630298827
    [Google Scholar]
  80. DaviesH. BignellG.R. CoxC. StephensP. EdkinsS. CleggS. TeagueJ. WoffendinH. GarnettM.J. BottomleyW. DavisN. DicksE. EwingR. FloydY. GrayK. HallS. HawesR. HughesJ. KosmidouV. MenziesA. MouldC. ParkerA. StevensC. WattS. HooperS. WilsonR. JayatilakeH. GustersonB.A. CooperC. ShipleyJ. HargraveD. Pritchard-JonesK. MaitlandN. Chenevix-TrenchG. RigginsG.J. BignerD.D. PalmieriG. CossuA. FlanaganA. NicholsonA. HoJ.W.C. LeungS.Y. YuenS.T. WeberB.L. SeiglerH.F. DarrowT.L. PatersonH. MaraisR. MarshallC.J. WoosterR. StrattonM.R. FutrealP.A. Mutations of the BRAF gene in human cancer.Nature2002417689294995410.1038/nature0076612068308
    [Google Scholar]
  81. MercerK.E. PritchardC.A. Raf proteins and cancer: B-Raf is identified as a mutational target.Biochim. Biophys. Acta Rev. Cancer200316531254010.1016/S0304‑419X(03)00016‑712781369
    [Google Scholar]
  82. MelckA.L. YipL. CartyS.E. The utility of BRAF testing in the management of papillary thyroid cancer.Oncologist201015121285129310.1634/theoncologist.2010‑015621147872
    [Google Scholar]
  83. ProiettiI. SkrozaN. MicheliniS. MambrinA. BalduzziV. BernardiniN. MarchesielloA. TolinoE. VolpeS. MaddalenaP. Di FraiaM. ManginoG. RomeoG. PotenzaC. BRAF inhibitors: molecular targeting and immunomodulatory actions.Cancers (Basel)2020127182310.3390/cancers1207182332645969
    [Google Scholar]
  84. HanJ. WuJ. SilkeJ. An overview of mammalian p38 mitogen-activated protein kinases, central regulators of cell stress and receptor signaling.F1000Res.20209F1000 Faculty Rev-65310.12688/f1000research.22092.1
    [Google Scholar]
  85. ZarubinT. HanJ. Activation and signaling of the p38 MAP kinase pathway.Cell Res.2005151111810.1038/sj.cr.729025715686620
    [Google Scholar]
  86. CanovasB. NebredaA.R. Diversity and versatility of p38 kinase signalling in health and disease.Nat. Rev. Mol. Cell Biol.202122534636610.1038/s41580‑020‑00322‑w33504982
    [Google Scholar]
  87. BordersA.S. de AlmeidaL. Van EldikL.J. WattersonD.M. The p38α mitogen-activated protein kinase as a central nervous system drug discovery target.BMC Neurosci.20089S2Suppl. 2S1210.1186/1471‑2202‑9‑S2‑S1219090985
    [Google Scholar]
  88. YoussifB.G.M. GoudaA.M. MoustafaA.H. AbdelhamidA.A. GomaaH.A.M. KamalI. MarzoukA.A. Design and synthesis of new triarylimidazole derivatives as dual inhibitors of BRAFV600E/p38α with potential antiproliferative activity.J. Mol. Struct.2022125313221810.1016/j.molstruc.2021.132218
    [Google Scholar]
  89. OcchipintiR. BoronW.F. Role of carbonic anhydrases and inhibitors in acid–base physiology: insights from mathematical modeling.Int. J. Mol. Sci.20192015384110.3390/ijms2015384131390837
    [Google Scholar]
  90. SupuranC.T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators.Nat. Rev. Drug Discov.20087216818110.1038/nrd246718167490
    [Google Scholar]
  91. KrasavinM. ShetnevA. SharonovaT. BaykovS. KalininS. NocentiniA. SharoykoV. PoliG. TuccinardiT. PresnukhinaS. TennikovaT.B. SupuranC.T. Continued exploration of 1,2,4-oxadiazole periphery for carbonic anhydrase-targeting primary arene sulfonamides: Discovery of subnanomolar inhibitors of membrane-bound hCA IX isoform that selectively kill cancer cells in hypoxic environment.Eur. J. Med. Chem.20191649210510.1016/j.ejmech.2018.12.04930594030
    [Google Scholar]
  92. FurmanD. CampisiJ. VerdinE. Carrera-BastosP. TargS. FranceschiC. FerrucciL. GilroyD.W. FasanoA. MillerG.W. MillerA.H. MantovaniA. WeyandC.M. BarzilaiN. GoronzyJ.J. RandoT.A. EffrosR.B. LuciaA. KleinstreuerN. SlavichG.M. Chronic inflammation in the etiology of disease across the life span.Nat. Med.201925121822183210.1038/s41591‑019‑0675‑031806905
    [Google Scholar]
  93. CharlierC. MichauxC. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs.Eur. J. Med. Chem.2003387-864565910.1016/S0223‑5234(03)00115‑612932896
    [Google Scholar]
  94. ClàriaJ. Cyclooxygenase-2 Biology.Curr. Pharm. Des.20039272177219010.2174/138161203345405414529398
    [Google Scholar]
  95. LuoY. JinM. LouL. YangS. LiC. LiX. ZhouM. CaiC. Role of arachidonic acid lipoxygenase pathway in Asthma.Prostaglandins Other Lipid Mediat.202215810660910.1016/j.prostaglandins.2021.10660934954219
    [Google Scholar]
  96. LiarasK. FesatidouM. GeronikakiA. Thiazoles and Thiazolidinones as COX/LOX Inhibitors.Molecules201823368510.3390/molecules2303068529562646
    [Google Scholar]
  97. YoussifB.G.M. MohamedM.F.A. Al-SaneaM.M. MoustafaA.H. AbdelhamidA.A. GomaaH.A.M. Novel aryl carboximidamide and 3-aryl-1,2,4-oxadiazole analogues of naproxen as dual selective COX-2/15-LOX inhibitors: Design, synthesis and docking studies.Bioorg. Chem.20198557758410.1016/j.bioorg.2019.02.04330878890
    [Google Scholar]
  98. BogdanC. Nitric oxide and the immune response.Nat. Immunol.200121090791610.1038/ni1001‑90711577346
    [Google Scholar]
  99. MillerM.J.S. ThompsonJ.H. ZhangX.J. Sadowska-KrowickaH. KakkisJ.L. MunshiU.K. SandovalM. RossiJ.L. Eloby-ChildressS. BeckmanJ.S. YeY.Z. RodiC.P. ManningP.T. CurrieM.G. ClarkD.A. Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis.Gastroenterology199510951475148310.1016/0016‑5085(95)90633‑97557128
    [Google Scholar]
  100. RicciottiE. FitzGeraldG.A. Prostaglandins and Inflammation.Arterioscler. Thromb. Vasc. Biol.2011315986100010.1161/ATVBAHA.110.20744921508345
    [Google Scholar]
  101. ArulselvanP. FardM.T. TanW.S. GothaiS. FakuraziS. NorhaizanM.E. KumarS.S. Role of antioxidants and natural products in inflammation.Oxid. Med. Cell. Longev.20162016527613010.1155/2016/5276130
    [Google Scholar]
  102. SabbataniS. FiorinoS. ManfrediR. The emerging of the fifth malaria parasite (Plasmodium knowlesi): A public health concern?Braz. J. Infect. Dis.201014329930910.1590/S1413‑8670201000030001920835518
    [Google Scholar]
  103. Dereje NigussieT.B. New targets in malaria parasite chemotherapy: a review.Malaria Contr. Eliminat201510.4172/2470‑6965/1000S1‑007
    [Google Scholar]
  104. WhiteN.J. The role of anti-malarial drugs in eliminating malaria.Malar. J.20087S1, S810.1186/1475‑2875‑7‑S1‑S819091042
    [Google Scholar]
  105. WarhurstD.C. SteeleJ.C.P. AdaguI.S. CraigJ.C. CullanderC. Hydroxychloroquine is much less active than chloroquine against chloroquine-resistant Plasmodium falciparum, in agreement with its physicochemical properties.J. Antimicrob. Chemother.200352218819310.1093/jac/dkg31912837731
    [Google Scholar]
  106. RosenthalP.J. Antimalarial drug discovery: old and new approaches.J. Exp. Biol.2003206213735374410.1242/jeb.0058914506208
    [Google Scholar]
  107. BergerO. OrtialS. WeinS. DenoyelleS. BressolleF. DurandT. EscaleR. VialH.J. Vo-HoangY. Evaluation of amidoxime derivatives as prodrug candidates of potent bis-cationic antimalarials.Bioorg. Med. Chem. Lett.201929162203220710.1016/j.bmcl.2019.06.04531255483
    [Google Scholar]
  108. AmorS. PeferoenL.A.N. VogelD.Y.S. BreurM. van der ValkP. BakerD. van NoortJ.M. Inflammation in neurodegenerative diseases – an update.Immunology2014142215116610.1111/imm.1223324329535
    [Google Scholar]
  109. KoliatsosV. AhmedF. LyketsosC. KortteK. RaoV. Neuropsychiatric disturbances associated with traumatic brain injury: a practical approach to evaluation and management.Semin. Neurol.201535106408210.1055/s‑0035‑154424125714869
    [Google Scholar]
  110. ReadyR.E. OttB.R. GraceJ. Cahn-WeinerD.A. Apathy and executive dysfunction in mild cognitive impairment and Alzheimer disease.Am. J. Geriatr. Psychiatry200311222222810.1097/00019442‑200303000‑0001312611752
    [Google Scholar]
  111. ChauhanV. ChauhanA. Oxidative stress in Alzheimer’s disease.Pathophysiology200613319520810.1016/j.pathophys.2006.05.00416781128
    [Google Scholar]
  112. AyoupM.S. BarakatM.R. Abdel-HamidH. EmamE. Al-FaiyzY.S. MasoudA.A. GhareebD.A. SonousiA. KassabA.E. Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-based derivatives as multitarget anti-Alzheimer agents.RSC Med. Chem.2024152080209710.1039/D4MD00113C
    [Google Scholar]
  113. AyoupM.S. GhanemM. Abdel-HamidH. Abu-SerieM.M. MasoudA. GhareebD.A. HawsawiM.B. SonousiA. KassabA.E. New 1,2,4-oxadiazole derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation.BMC Chem.202418113010.1186/s13065‑024‑01235‑x39003489
    [Google Scholar]
  114. LemonN. CanepaE. IliesM.A. FossatiS. Carbonic anhydrases as potential targets against neurovascular unit dysfunction in Alzheimer's disease and stroke.Front Aging Neurosci. 2021 Nov 16;13:20211377227810.3389/fnagi.2021.772278
    [Google Scholar]
  115. KucukogluK. FaydaliN. BulD. NadarogluH. SeverB. AltıntopM.D. OzturkB. GuzelI. Synthesis, in silico and in vitro evaluation of new 3,5-disubstituted-1,2,4-oxadiazole derivatives as carbonic anhydrase inhibitors and cytotoxic agents.J. Mol. Struct.2023127613469910.1016/j.molstruc.2022.134699
    [Google Scholar]
  116. ZarghiA. HajimahdiZ. Substituted oxadiazoles: A patent review (2010–2012).Expert Opin. Ther. Pat.20132391209123210.1517/13543776.2013.797409
    [Google Scholar]
  117. TestaL. AndreottiF. Biondi ZoccaiG.G.L. BurzottaF. BellocciF. CreaF. Ximelagatran/melagatran against conventional anticoagulation: A meta-analysis based on 22,639 patients.Int. J. Cardiol.2007122211712410.1016/j.ijcard.2006.11.04117222926
    [Google Scholar]
  118. SchulmanS. WåhlanderK. LundströmT. ClasonS.B. ErikssonH. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran.N. Engl. J. Med.2003349181713172110.1056/NEJMoa03010414585939
    [Google Scholar]
  119. PlasseT.F. DelgadoB. PottsJ. AbramsonD. FehrmannC. FathiR. McComseyG.A. A randomized, placebo-controlled pilot study of upamostat, a host-directed serine protease inhibitor, for outpatient treatment of COVID-19.Int. J. Infect. Dis.202312814815610.1016/j.ijid.2022.12.00336549549
    [Google Scholar]
  120. SongX. WangD. QuX. DongN. TengS. A meta-analysis of naldemedine for the treatment of opioid-induced constipation.Expert Rev. Clin. Pharmacol.201912212112810.1080/17512433.2019.157084530652502
    [Google Scholar]
  121. BakerD.E. Formulary drug review.Naldemedine. Hosp. Pharm.201752746446810.1177/001857871772480529276274
    [Google Scholar]
  122. SilvestriniB. PozzattiC. Pharmacological properties of 3‐phenyl‐5 β diethylaminoethyl‐1,2,4‐oxadiazole.Br. J. Pharmacol. Chemother.196116320921710.1111/j.1476‑5381.1961.tb01080.x19108149
    [Google Scholar]
  123. ZaikenK. ChengJ.W.M. Azilsartan medoxomil: a new Angiotensin receptor blocker.Clin. Ther.201133111577158910.1016/j.clinthera.2011.10.00722071238
    [Google Scholar]
  124. PerryC.M. Azilsartan medoxomil: A review of its use in hypertension.Clin. Drug Investig.20123262163910.1007/BF03261917
    [Google Scholar]
  125. MiuraS. OkabeA. MatsuoY. KarnikS.S. SakuK. Unique binding behavior of the recently approved angiotensin II receptor blocker azilsartan compared with that of candesartan.Hypertens. Res.201336213413910.1038/hr.2012.14723034464
    [Google Scholar]
  126. HaasM. VlcekV. BalabanovP. SalmonsonT. BakchineS. MarkeyG. WeiseM. Schlosser-WeberG. BrohmannH. YerroC.P. MendizabalM.R. Stoyanova-BeninskaV. HillegeH.L. European Medicines Agency review of ataluren for the treatment of ambulant patients aged 5 years and older with Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene.Neuromuscul. Disord.201525151310.1016/j.nmd.2014.11.01125497400
    [Google Scholar]
  127. RoyB. FriesenW.J. TomizawaY. LeszykJ.D. ZhuoJ. JohnsonB. DakkaJ. TrottaC.R. XueX. MutyamV. KeelingK.M. MobleyJ.A. RoweS.M. BedwellD.M. WelchE.M. JacobsonA. Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression.Proc. Natl. Acad. Sci. USA201611344125081251310.1073/pnas.160533611327702906
    [Google Scholar]
  128. FinkelR.S. Read-through strategies for suppression of nonsense mutations in Duchenne/Becker muscular dystrophy: aminoglycosides and ataluren (PTC124).J. Child Neurol.20102591158116410.1177/088307381037112920519671
    [Google Scholar]
  129. RowanC. UngaroR. MehandruS. ColombelJ.F. An overview of ozanimod as a therapeutic option for adults with moderate-to-severe active ulcerative colitis.Expert Opin. Pharmacother.202223889390410.1080/14656566.2022.207160535503955
    [Google Scholar]
  130. DumitrescuL. PapathanasiouA. CoclituC. GarjaniA. EvangelouN. ConstantinescuC.S. PopescuB.O. TanasescuR. An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis.Expert Opin. Pharmacother.202324449550910.1080/14656566.2023.217889836946625
    [Google Scholar]
  131. McGinleyM.P. CohenJ.A. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions.Lancet2021398103061184119410.1016/S0140‑6736(21)00244‑034175020
    [Google Scholar]
  132. AnnusÁ. VécseiL. Spotlight on opicapone as an adjunct to levodopa in Parkinson’s disease: Design, development and potential place in therapy.Drug Des. Devel. Ther.20171114315110.2147/DDDT.S10422728123288
    [Google Scholar]
  133. BergerA.A. WinnickA. IzygonJ. JacobB.M. KayeJ.S. KayeR.J. NeuchatE.E. KayeA.M. AlpaughE.S. CornettE.M. HanA.H. KayeA.D. Opicapone, a novel catechol-o-methyl transferase inhibitor, for treatment of parkinson’s disease “off” episodes.Health Psychol. Res.20221053607410.52965/001c.3607435774903
    [Google Scholar]
/content/journals/lddd/10.2174/0115701808349648241204054857
Loading
/content/journals/lddd/10.2174/0115701808349648241204054857
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): 1,2,4-oxadiazoles; Amidoximes; anti-inflammatory; antibacterial; anticancer; nitric oxide
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