Skip to content
2000
Volume 25, Issue 9
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Hydantoin, a five-membered heterocyclic scaffold, is regarded as a crucial scaffold in medicinal chemistry. Hydantoins have been useful in synthesizing medicines like nilutamide, enzalutamide, and apalutamide. Thiohydantoin and selenohydantoin have been discovered as two separate types of hydantoin. There are two hydrogen bond donors, two hydrogen bond acceptors, and four substitution sites. These characteristics have led to the design, synthesis, and expansion of hydantoin derivatives' biological and pharmacological effects against numerous types of malignancies. This study reviews the recent contributions of hydantoin and its isosteric variants to medicinal chemistry. To emphasize their significance, certain significant compounds based on hydantoins and their structure activity relationships (SAR) are briefly discussed. We thoroughly analyzed each scaffolds' structural characteristics and SAR, and these scaffolds may one day show potential anticancer activities.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575329643241206101210
2025-01-10
2025-10-10

  • From This Site

    /content/journals/mrmc/10.2174/0113895575329643241206101210
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BrayF. LaversanneM. WeiderpassE. SoerjomataramI. The ever‐increasing importance of cancer as a leading cause of premature death worldwide.Cancer2021127163029303010.1002/cncr.33587 34086348
     [Google Scholar]
  2. ChenS. CaoZ. PrettnerK. KuhnM. YangJ. JiaoL. WangZ. LiW. GeldsetzerP. BärnighausenT. BloomD.E. WangC. Estimates and projections of the global economic cost of 29 cancers in 204 countries and territories from 2020 to 2050.JAMA Oncol.20239446547210.1001/jamaoncol.2022.7826 36821107
     [Google Scholar]
  3. GuidaF. KidmanR. FerlayJ. SchüzJ. SoerjomataramI. KithakaB. GinsburgO. Mailhot VegaR.B. GalukandeM. ParhamG. VaccarellaS. CanfellK. IlbawiA.M. AndersonB.O. BrayF. dos-Santos-SilvaI. McCormackV. Global and regional estimates of orphans attributed to maternal cancer mortality in 2020.Nat. Med.202228122563257210.1038/s41591‑022‑02109‑2 36404355
     [Google Scholar]
  4. FerlayJ. ErvikM. LamF. LaversanneM. ColombetM. MeryL. PiñerosM. ZnaorA. SoerjomataramI. BrayF. Global Cancer Observatory: Cancer Today.Lyon, FranceInternational Agency for Research on Cancer2024
     [Google Scholar]
  5. FerlayJ. ColombetM. SoerjomataramI. ParkinD.M. PiñerosM. ZnaorA. BrayF. Cancer statistics for the year 2020: An overview.Int. J. Cancer2021149477878910.1002/ijc.33588 33818764
     [Google Scholar]
  6. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  7. AliI. LoneM. Al-OthmanZ. Al-WarthanA. SanagiM. Heterocyclic scaffolds: Centrality in anticancer drug development.Curr. Drug Targets201516771173410.2174/1389450116666150309115922 25751009
     [Google Scholar]
  8. JampilekJ. Heterocycles in medicinal chemistry.Molecules20192421383910.3390/molecules24213839 31731387
     [Google Scholar]
  9. HamamaW.S. IsmailM.A. SolimanM. ShaabanS. ZoorobH.H. Behavior of 2‐iminothiazolidin‐4‐one with different reagents.J. Heterocycl. Chem.20114851169117410.1002/jhet.628
     [Google Scholar]
  10. Abdel-WahabB. ShaabanS. Thiazolothiadiazoles and thiazolooxadiazoles: Synthesis and biological applications.Synthesis201446131709171610.1055/s‑0033‑1338627
     [Google Scholar]
  11. SayedA.R. Al-FaiyzY.S. ElsawyH. ShaabanS. MohamedM.A. Synthesis and biochemical studies of novel Mon-Azothiazoles and Bis-Azothiazoles based on 2-(4-(Dimethylamino)Benzylidene)Hydrazine-1-Carbothioamide.Polycycl. Aromat. Compd.20234332644265510.1080/10406638.2022.2049326
     [Google Scholar]
  12. MeuselM. GütschowM. Recent developments in hydantoin chemistry. A review.Org. Prep. Proced. Int.200436539144310.1080/00304940409356627
     [Google Scholar]
  13. ChoS. KimS.H. ShinD. Recent applications of hydantoin and thiohydantoin in medicinal chemistry.Eur. J. Med. Chem.201916451754510.1016/j.ejmech.2018.12.066 30622025
     [Google Scholar]
  14. MezoughiA.B. MohammedW.A. EttarhouniZ.O. Recent biological applications and chemical synthesis of Thiohydantoins.J. Chem. Rev.20211319621810.22034/jcr.2021.285244.1111
     [Google Scholar]
  15. KumarV. Designed synthesis of diversely substituted hydantoins and hydantoin-based hybrid molecules: A personal account.Synlett202132191897191010.1055/a‑1480‑6474
     [Google Scholar]
  16. WareE. The chemistry of the hydantoins.Chem. Rev.195046340347010.1021/cr60145a001 24537833
     [Google Scholar]
  17. SallamA.A. MohyeldinM.M. FoudahA.I. AklM.R. NazzalS. MeyerS.A. LiuY.Y. El SayedK.A. Marine natural products-inspired phenylmethylene hydantoins with potent in vitro and in vivo antitumor activities via suppression of Brk and FAK signaling.Org. Biomol. Chem.201412285295530310.1039/C4OB00553H 24927150
     [Google Scholar]
  18. LitonA.K. IslamM.R. Synthesis of hydantoin and thiohydantoin related compounds from benzil and study of their cytotoxicity.Bangladesh J. Pharmacol.200811101510.3329/bjp.v1i1.481
     [Google Scholar]
  19. ZhangM. LiangY.R. LiH. LiuM.M. WangY. Design, synthesis, and biological evaluation of hydantoin bridged analogues of combretastatin A-4 as potential anticancer agents.Bioorg. Med. Chem.201725246623663410.1016/j.bmc.2017.10.045 29126741
     [Google Scholar]
  20. XieH. LiangJ.J. WangY.L. HuT.X. WangJ.Y. YangR.H. YanJ.K. ZhangQ.R. XuX. LiuH.M. KeY. The design, synthesis and anti-tumor mechanism study of new androgen receptor degrader.Eur. J. Med. Chem.202020411251210.1016/j.ejmech.2020.112512 32736229
     [Google Scholar]
  21. JungM.E. OukS. YooD. SawyersC.L. ChenC. TranC. WongvipatJ. Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC).J. Med. Chem.20105372779279610.1021/jm901488g 20218717
     [Google Scholar]
  22. ZhangN. MaS. Recent development of membrane-active molecules as antibacterial agents.Eur. J. Med. Chem.201918411174310.1016/j.ejmech.2019.111743 31586478
     [Google Scholar]
  23. HandzlikJ. SzymańskaE. ChevalierJ. OtrębskaE. Kieć-KononowiczK. PagèsJ.M. AlibertS. Amine–alkyl derivatives of hydantoin: New tool to combat resistant bacteria.Eur. J. Med. Chem.201146125807581610.1016/j.ejmech.2011.09.032 22000919
     [Google Scholar]
  24. FujisakiF. ShojiK. ShimodouzonoM. KashigeN. MiakeF. SumotoK. Antibacterial activity of 5-dialkylaminomethylhydantoins and related compounds.Chem. Pharm. Bull. (Tokyo)20105881123112610.1248/cpb.58.1123 20686274
     [Google Scholar]
  25. SondhiS.M. SinghJ. KumarA. JamalH. GuptaP.P. Synthesis of amidine and amide derivatives and their evaluation for anti-inflammatory and analgesic activities.Eur. J. Med. Chem.20094431010101510.1016/j.ejmech.2008.06.029 18701196
     [Google Scholar]
  26. LesuisseD. MaugerJ. NemecekC. MaignanS. BoiziauJ. HarlowG. HittingerA. RufS. StrobelH. NairA. RitterK. MalleronJ.L. DagallierA. El-AhmadY. GuilloteauJ.P. GuizaniH. BouchardH. VenotC. Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: Advantages in comparison with competitive inhibitors.Bioorg. Med. Chem. Lett.20112182224222810.1016/j.bmcl.2011.03.003 21441024
     [Google Scholar]
  27. SergentD. WangQ. SasakiN.A. OuazzaniJ. Synthesis of hydantoin analogues of (2S,3R,4S)-4-hydroxyisoleucine with insulinotropic properties.Bioorg. Med. Chem. Lett.200818154332433510.1016/j.bmcl.2008.06.081 18621529
     [Google Scholar]
  28. GhasempourL. AsghariS. TajbakhshM. MohseniM. One‐pot synthesis of new hydantoin (thiohydantoin) derivatives and evaluation of their antibacterial and antioxidant activities.J. Heterocycl. Chem.202057124136414810.1002/jhet.4120
     [Google Scholar]
  29. MarzoukA.A. BassA.K.A. AhmedM.S. AbdelhamidA.A. ElshaierY.A.M.M. SalmanA.M.M. AlyO.M. Design, synthesis and anticonvulsant activity of new imidazolidindione and imidazole derivatives.Bioorg. Chem.202010110402010.1016/j.bioorg.2020.104020 32599366
     [Google Scholar]
  30. ZhuQ. PanY. XuZ. LiR. QiuG. XuW. KeX. WuL. HuX. Synthesis and potential anticonvulsant activity of new N-3-substituted 5,5-cyclopropanespirohydantoins.Eur. J. Med. Chem.200944129630210.1016/j.ejmech.2008.02.024 18396358
     [Google Scholar]
  31. StilzH.U. GubaW. JablonkaB. JustM. KlinglerO. KönigW. WehnerV. ZollerG. Discovery of an orally active non-peptide fibrinogen receptor antagonist based on the hydantoin scaffold.J. Med. Chem.20014481158117610.1021/jm001068s 11312916
     [Google Scholar]
  32. PękalaE. StadnickaK. BrodaA. ZygmuntM. FilipekB. Kieć-KononowiczK. Synthesis, structure–activity relationship of some new anti-arrhythmic 5-arylidene imidazolidine-2,4-dione derivatives.Eur. J. Med. Chem.200540325926910.1016/j.ejmech.2004.11.006 15725495
     [Google Scholar]
  33. Kieć-KononowiczK. StadnickaK. MitkaA. PekalaE. FilipekB. SapaJ. ZygmuntM. Synthesis, structure and antiarrhythmic properties evaluation of new basic derivatives of 5,5-diphenylhydantoin.Eur. J. Med. Chem.200338655556610.1016/S0223‑5234(03)00075‑8 12832127
     [Google Scholar]
  34. NishinamiS. IkedaK. NagaoT. KoyamaA.H. ArakawaT. ShirakiK. Aromatic interaction of hydantoin compounds leads to virucidal activities.Biophys. Chem.202127510662110.1016/j.bpc.2021.106621 34004504
     [Google Scholar]
  35. KimD. WangL. CaldwellC.G. ChenP. FinkeP.E. OatesB. MacCossM. MillsS.G. MalkowitzL. GouldS.L. DeMartinoJ.A. SpringerM.S. HazudaD. MillerM. KesslerJ. DanzeisenR. CarverG. CarellaA. HolmesK. LinebergerJ. SchleifW.A. EminiE.A. Design, synthesis, and SAR of heterocycle-containing antagonists of the human CCR5 receptor for the treatment of HIV-1 infection.Bioorg. Med. Chem. Lett.200111243103310610.1016/S0960‑894X(01)00655‑2 11720852
     [Google Scholar]
  36. NiqueF. HebbeS. TriballeauN. PeixotoC. LefrançoisJ.M. JaryH. AlveyL. ManiocM. HoussemanC. KlaassenH. Van BeeckK. GuédinD. NamourF. MinetD. Van der AarE. FeyenJ. FletcherS. BlanquéR. Robin-JagerschmidtC. DeprezP. Identification of a 4-(hydroxymethyl)diarylhydantoin as a selective androgen receptor modulator.J. Med. Chem.201255198236824710.1021/jm300281x 22957947
     [Google Scholar]
  37. LiJ.J. IulaD.M. NguyenM.N. HuL.Y. DettlingD. JohnsonT.R. DuD.Y. ShanmugasundaramV. Van CampJ.A. WangZ. HarterW.G. YueW.S. BoysM.L. WadeK.J. DrummondE.M. SamasB.M. LefkerB.A. HogeG.S. LovdahlM.J. AsbillJ. CarrollM. MeadeM.A. CiottiS.M. Krieger-BurkeT. Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen receptor antagonist devoid of phototoxicity for dermatological indications.J. Med. Chem.200851217010701410.1021/jm8009316 18921992
     [Google Scholar]
  38. HeY. HwangD.J. PonnusamyS. ThiyagarajanT. MohlerM.L. NarayananR. MillerD.D. Exploration and biological evaluation of basic heteromonocyclic propenamide derivatives as sards for the treatment of enzalutamide-resistant prostate cancer.J. Med. Chem.20216415110451106210.1021/acs.jmedchem.1c00439 34269581
     [Google Scholar]
  39. HeY. HwangD.J. PonnusamyS. ThiyagarajanT. MohlerM.L. NarayananR. MillerD.D. Pyrazol-1-yl-propanamides as SARD and pan-antagonists for the treatment of enzalutamide-resistant prostate cancer.J. Med. Chem.20206321126421266510.1021/acs.jmedchem.0c00943 33095584
     [Google Scholar]
  40. ZhangZ. ConnollyP.J. LimH.K. PandeV. MeerpoelL. TelehaC. BranchJ.R. OndrusJ. HicksonI. BushT. LuistroL. PackmanK. BischoffJ.R. IbrahimS. ParrettC. ChongY. GottardisM.M. BignanG. Discovery of JNJ-63576253: A clinical stage androgen receptor antagonist for F877L mutant and wild-type castration-resistant prostate cancer (mCRPC).J. Med. Chem.202164290992410.1021/acs.jmedchem.0c01563 33470111
     [Google Scholar]
  41. FlickA.C. LeverettC.A. DingH.X. McInturffE. FinkS.J. HelalC.J. DeForestJ.C. MorseP.D. MahapatraS. O’DonnellC.J. Synthetic approaches to new drugs approved during 2018.J. Med. Chem.20206319106521070410.1021/acs.jmedchem.0c00345 32338902
     [Google Scholar]
  42. WuX. FengW. YangM. LiuX. GaoM. LiX. GanL. HeT. HC-1119, a deuterated Enzalutamide, inhibits migration, invasion and metastasis of the AR-positive triple-negative breast cancer cells.Mol. Biol. Rep.202249109231924010.1007/s11033‑022‑07749‑8 35960413
     [Google Scholar]
  43. LiX. ChengK. LiX. ZhouY. LiuJ. ZengH. ChenY. LiuX. ZhangY. WangY. BiF. ZhengL. Phase I clinical trial of HC‐1119: A deuterated form of enzalutamide.Int. J. Cancer202114971473148210.1002/ijc.33706 34109624
     [Google Scholar]
  44. KonnertL. LamatyF. MartinezJ. ColacinoE. Recent advances in the synthesis of Hydantoins: The state of the art of a valuable scaffold.Chem. Rev.201711723137571380910.1021/acs.chemrev.7b00067 28644621
     [Google Scholar]
  45. BlackadarC.B. Historical review of the causes of cancer.World J. Clin. Oncol.201671548610.5306/wjco.v7.i1.54 26862491
     [Google Scholar]
  46. SudaniB.R. The multifaceted biological activities of Hydantoin derivatives: From antimicrobial to anticancer agents.Bioscan202419889210.63001/tbs.2024.v19.i02.S2.pp
     [Google Scholar]
  47. SunilD. KamathP. Multi-target directed indole based hybrid molecules in cancer therapy: An up-to-date evidence-based review.Curr. Top. Med. Chem.201717995998510.2174/1568026616666160927150839 27697057
     [Google Scholar]
  48. PettitG.R. HeraldC.L. LeetJ.E. GuptaR. SchaufelbergerD.E. BatesR.B. ClewlowP.J. DoubekD.L. ManfrediK.P. RützlerK. SchmidtJ.M. TackettL.P. WardF.B. BruckM. CamouF. Antineoplastic agents. 168. Isolation and structure of axinohydantoin.Can. J. Chem.19906891621162410.1139/v90‑250
     [Google Scholar]
  49. NishizukaY. The role of protein kinase C in cell surface signal transduction and tumour promotion.Nature1984308596169369810.1038/308693a0 6232463
     [Google Scholar]
  50. PatilA.D. FreyerA.J. KillmerL. HofmannG. JohnsonR.K. Z-Axinohydantoin and Debromo-Z-Axinohydantoin from the sponge Stylotella aurantium: Inhibitors of protein kinase C.Nat. Prod. Lett.19979320120710.1080/10575639708048315
     [Google Scholar]
  51. CastilloA. JusticeM.J. The kinesin related motor protein, Eg5, is essential for maintenance of pre-implantation embryogenesis.Biochem. Biophys. Res. Commun.2007357369469910.1016/j.bbrc.2007.04.021 17449012
     [Google Scholar]
  52. WaitzmanJ.S. RiceS.E. Mechanism and regulation of kinesin‐5, an essential motor for the mitotic spindle.Biol. Cell2014106111210.1111/boc.201300054 24125467
     [Google Scholar]
  53. HothaS. YarrowJ.C. YangJ.G. GarrettS. RenduchintalaK.V. MayerT.U. KapoorT.M. HR22C16: A potent small-molecule probe for the dynamics of cell division.Angew. Chem. Int. Ed.200342212379238210.1002/anie.200351173 12783501
     [Google Scholar]
  54. BarnesD.W. Growth characteristics of A431 human epidermoid carcinoma cells in serum-free medium: Inhibition by epidermal growth factor.Adv. Exp. Med. Biol.1984172496610.1007/978‑1‑4615‑9376‑8_4 6610292
     [Google Scholar]
  55. WykoskyJ. FentonT. FurnariF. CaveneeW.K. Therapeutic targeting of epidermal growth factor receptor in human cancer: Successes and limitations.Chin. J. Cancer201130151210.5732/cjc.010.10542 21192840
     [Google Scholar]
  56. CarmiC. CavazzoniA. ZulianiV. LodolaA. BordiF. PlazziP.V. AlfieriR.R. PetroniniP.G. MorM. 5-benzylidene-hydantoins as new EGFR inhibitors with antiproliferative activity.Bioorg. Med. Chem. Lett.200616154021402510.1016/j.bmcl.2006.05.010
     [Google Scholar]
  57. CavazzoniA. AlfieriR.R. CarmiC. ZulianiV. GalettiM. FumarolaC. FrazziR. BonelliM. BordiF. LodolaA. MorM. PetroniniP.G. Dual mechanisms of action of the 5-benzylidene-hydantoin UPR1024 on lung cancer cell lines.Mol. Cancer Ther.20087236137010.1158/1535‑7163.MCT‑07‑0477 18281519
     [Google Scholar]
  58. El-DeebI.M. BayoumiS.M. El-SherbenyM.A. Abdel-AzizA.A.M. Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction.Eur. J. Med. Chem.20104562516253010.1016/j.ejmech.2010.02.038 20236733
     [Google Scholar]
  59. ZhaoE. HouJ. KeX. AbbasM.N. KausarS. ZhangL. CuiH. The roles of sirtuin family proteins in cancer progression.Cancers 20191112194910.3390/cancers11121949 31817470
     [Google Scholar]
  60. SacconnayL. RyckewaertL. RandazzoG.M. PetitC. PassosC.D.S. JachnoJ. MichailovienėV. ZubrienėA. MatulisD. CarruptP.A. Simões-PiresC.A. NurissoA. 5-Benzylidene-hydantoin is a new scaffold for SIRT inhibition: From virtual screening to activity assays.Eur. J. Pharm. Sci.201685596710.1016/j.ejps.2016.01.010 26791955
     [Google Scholar]
  61. PustenkoA. NocentiniA. GratteriP. BonardiA. VoznyI. ŽalubovskisR. SupuranC.T. The antibiotic furagin and its derivatives are isoform-selective human carbonic anhydrase inhibitors.J. Enzyme Inhib. Med. Chem.20203511011102010.1080/14756366.2020.1752201 32297543
     [Google Scholar]
  62. LannuzelM. LamotheM. SchambelP. EtiévantC. HillB. PerezM. From pure FPP to mixed FPP and CAAX competitive inhibitors of farnesyl protein transferase.Bioorg. Med. Chem. Lett.20031381459146210.1016/S0960‑894X(03)00171‑9 12668012
     [Google Scholar]
  63. RajabiM. MansellD. FreemanS. BryceR.A. Structure–activity relationship of 2,4,5-trioxoimidazolidines as inhibitors of thymidine phosphorylase.Eur. J. Med. Chem.20114641165117110.1016/j.ejmech.2011.01.035 21324566
     [Google Scholar]
  64. LiangX. FuH. XiaoP. FangH. HouX. Design, synthesis and biological evaluation of imidazolidine-2,4-dione and 2-thioxothiazolidin-4-one derivatives as lymphoid-specific tyrosine phosphatase inhibitors.Bioorg. Chem.202010310412410.1016/j.bioorg.2020.104124 32768742
     [Google Scholar]
  65. RajicZ. ZorcB. Raic-MalicS. EsterK. KraljM. PavelicK. BalzariniJ. De ClercqE. MintasM. Hydantoin derivatives of L- and D-amino acids: synthesis and evaluation of their antiviral and antitumoral activity.Molecules2006111183784810.3390/11110837 18007390
     [Google Scholar]
  66. GravesB. ThompsonT. XiaM. JansonC. LukacsC. DeoD. Di LelloP. FryD. GarvieC. HuangK.S. GaoL. TovarC. LoveyA. WannerJ. VassilevL.T. Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization.Proc. Natl. Acad. Sci. USA201210929117881179310.1073/pnas.1203789109 22745160
     [Google Scholar]
  67. WangG. WangY. WangL. HanL. HouX. FuH. FangH. Design, synthesis and preliminary bioactivity studies of imidazolidine-2,4-dione derivatives as Bcl-2 inhibitors.Bioorg. Med. Chem.201523237359736510.1016/j.bmc.2015.10.023 26558516
     [Google Scholar]
  68. LiuJ. ZhangK. MaiX. WeiJ. LiaoY. ZhongY. LiuY. FengL. LiuC. Synthesis, anticancer evaluation and docking study of 3-benzyloxyhydantoin derivatives.Med. Chem.2016121374710.2174/1573406411666150708111631 26152144
     [Google Scholar]
  69. ZhongB. VatolinS. IdippilyN.D. LamaR. AlhadadL.A. ReuF.J. SuB. Structural optimization of non-nucleoside DNA methyltransferase inhibitor as anti-cancer agent.Bioorg. Med. Chem. Lett.20162641272127510.1016/j.bmcl.2016.01.020 26774653
     [Google Scholar]
  70. LaskoL.M. JakobC.G. EdaljiR.P. QiuW. MontgomeryD. DigiammarinoE.L. HansenT.M. RisiR.M. FreyR. ManavesV. ShawB. AlgireM. HesslerP. LamL.T. UzielT. FaivreE. FergusonD. BuchananF.G. MartinR.L. TorrentM. ChiangG.G. KarukurichiK. LangstonJ.W. WeinertB.T. ChoudharyC. de VriesP. KlugeA.F. PataneM.A. Van DrieJ.H. WangC. McElligottD. KesickiE. MarmorsteinR. SunC. ColeP.A. RosenbergS.H. MichaelidesM.R. LaiA. BrombergK.D. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.Nature2017550767412813210.1038/nature24028 28953875
     [Google Scholar]
  71. HarrasM.F. SabourR. Design, synthesis and biological evaluation of novel 1,3,4-trisubstituted pyrazole derivatives as potential chemotherapeutic agents for hepatocellular carcinoma.Bioorg. Chem.20187814915710.1016/j.bioorg.2018.03.014 29567429
     [Google Scholar]
  72. ObradovićA. MatićM. OgnjanovićB. ĐurđevićP. MarinkovićE. UšćumlićG. BožićB. Božić NedeljkovićB. Antiproliferative and antimigratory effects of 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives in human breast cancer cells.Saudi Pharm. J.202028324625410.1016/j.jsps.2020.01.003 32194325
     [Google Scholar]
  73. RothH.S. HergenrotherP.J. Derivatives of procaspase-activating compound 1 (PAC-1) and their anticancer activities.Curr. Med. Chem.201623320124110.2174/0929867323666151127201829 26630918
     [Google Scholar]
  74. FurutachiM. OtaK. FujisakiF. IkedaR. YoshikawaN. YokotaT. TakedaY. YokomizoK. ZhouJ.R. KashigeN. MiakeF. SumotoK. Anti-proliferative activities of some bivalent symmetrical 5-substituted hydantoin derivatives towards human brain glioma U251 cells (U251) and human carcinoma cells (KB3-1).Biol. Pharm. Bull.201942111953195610.1248/bpb.b19‑00486 31685778
     [Google Scholar]
  75. McNallyV.A. GbajA. DouglasK.T. StratfordI.J. JaffarM. FreemanS. BryceR.A. Identification of a novel class of inhibitor of human and Escherichia coli thymidine phosphorylase by in silico screening.Bioorg. Med. Chem. Lett.200313213705370910.1016/j.bmcl.2003.08.010 14552762
     [Google Scholar]
  76. TrisovicN. BozicB. ObradovicA. StefanovicO. MarkovicS. ComicL. BozicB. UscumlicG. Structure-activity relationships of 3-substituted-5,5- diphenylhydantoins as potential antiproliferative and antimicrobial agents.J. Serb. Chem. Soc.201176121597160610.2298/JSC110314143T
     [Google Scholar]
  77. AlanaziA.M. El-AzabA.S. Al-SwaidanI.A. MaaroufA.R. El-BendaryE.R. Abu El-EninM.A. Abdel-AzizA.A.M. Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives.Med. Chem. Res.201322126129614210.1007/s00044‑013‑0597‑1
     [Google Scholar]
  78. HmudaS. TrišovićN. RoganJ. PoletiD. VitnikŽ. VitnikV. ValentićN. BožićB. UšćumlićG. New derivatives of hydantoin as potential antiproliferative agents: Biological and structural characterization in combination with quantum chemical calculations.Monatsh. Chem.2014145582183310.1007/s00706‑013‑1149‑6
     [Google Scholar]
  79. ŻesławskaE. KincsesA. SpenglerG. NitekW. WyrzucK. Kieć-KononowiczK. HandzlikJ. The 5-aromatic hydantoin-3-acetate derivatives as inhibitors of the tumour multidrug resistance efflux pump P-glycoprotein (ABCB1): Synthesis, crystallographic and biological studies.Bioorg. Med. Chem.201624122815282210.1016/j.bmc.2016.04.055 27160056
     [Google Scholar]
  80. AlkahtaniH.M. AlanaziM.M. AleanizyF.S. AlqahtaniF.Y. AlhoshaniA. AlanaziF.E. AlmehiziaA.A. AbdallaA.N. AlanaziM.G. El-AzabA.S. Abdel-AzizA.A.M. Synthesis, anticancer, apoptosis-inducing activities and EGFR and VEGFR2 assay mechanistic studies of 5,5-diphenylimidazolidine-2,4-dione derivatives: Molecular docking studies.Saudi Pharm. J.201927568269310.1016/j.jsps.2019.04.003 31297023
     [Google Scholar]
  81. HassaninM.A. MustafaM. AbourehabM.A.S. HassanH.A. AlyO.M. BeshrE.A.M. Design and synthesis of new hydantoin acetanilide derivatives as anti-NSCLC targeting EGFRL858R/T790M mutations.Pharmaceuticals202215785710.3390/ph15070857 35890154
     [Google Scholar]
  82. LeeJ. KimJ. KohJ.S. ChungH.H. KimK.H. Hydantoin derivatives as non-peptidic inhibitors of Ras farnesyl transferase.Bioorg. Med. Chem. Lett.20061671954195610.1016/j.bmcl.2005.12.074 16442288
     [Google Scholar]
  83. AshrafH. A.; Dalal A, A-E.; Nermin S, A.; Bernard D, G.; Jose T, T.; Heather N, T.; Adam B, K.; Gary A, P. Synthesis of novel tadalafil analogues and their evaluation as phosphodiesterase inhibitors and anticancer agents.Arzneimittelforschung201159841542110.1055/s‑0031‑1296417 19813465
     [Google Scholar]
  84. AbadiA.H. GaryB.D. TinsleyH.N. PiazzaG.A. Abdel-HalimM. Synthesis, molecular modeling and biological evaluation of novel tadalafil analogues as phosphodiesterase 5 and colon tumor cell growth inhibitors, new stereochemical perspective.Eur. J. Med. Chem.20104541278128610.1016/j.ejmech.2009.10.046 20206015
     [Google Scholar]
  85. MohamedH.A. GirgisN.M.R. WilckenR. BauerM.R. TinsleyH.N. GaryB.D. PiazzaG.A. BoecklerF.M. AbadiA.H. Synthesis and molecular modeling of novel tetrahydro-β-carboline derivatives with phosphodiesterase 5 inhibitory and anticancer properties.J. Med. Chem.201154249550910.1021/jm100842v 21189023
     [Google Scholar]
  86. AbadiA.H. LehmannJ. PiazzaG.A. Abdel-HalimM. AliM.S.M. Synthesis, molecular modeling, and biological evaluation of novel tetrahydro-β-carboline hydantoin and tetrahydro-β-carboline thiohydantoin derivatives as phosphodiesterase 5 inhibitors.Int. J. Med. Chem.201120111910.1155/2011/562421 27471602
     [Google Scholar]
  87. AhmedN.S. AliA.H. El-NasharS.M. GaryB.D. FajardoA.M. TinsleyH.N. PiazzaG.A. NegriM. AbadiA.H. Exploring the PDE5 H-pocket by ensemble docking and structure-based design and synthesis of novel β-carboline derivatives.Eur. J. Med. Chem.20125732934310.1016/j.ejmech.2012.09.029 23117589
     [Google Scholar]
  88. ShankaraiahN. NekkantiS. ChudasamaK.J. SenwarK.R. SharmaP. JeengarM.K. NaiduV.G.M. SrinivasuluV. SrinivasuluG. KamalA. Design, synthesis and anticancer evaluation of tetrahydro-β-carboline-hydantoin hybrids.Bioorg. Med. Chem. Lett.201424235413541710.1016/j.bmcl.2014.10.038 25453799
     [Google Scholar]
  89. ZhengH. WuY. SunB. ChengC. QiaoY. JiangY. ZhaoS. XieZ. TanJ. LouH. Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect.Eur. J. Med. Chem.201815876778010.1016/j.ejmech.2018.09.028 30245400
     [Google Scholar]
  90. YaoC.H. HsiehT.C. SongJ.S. LeeJ.C. Design, synthesis and anticancer evaluation of β-carboline-1-one hydantoins.Future Med. Chem.202012318319210.4155/fmc‑2019‑0276 31813284
     [Google Scholar]
  91. Basappa; Ananda Kumar, C.S.; Nanjunda Swamy, S.; Sugahara, K.; Rangappa, K.S. Anti-tumor and anti-angiogenic activity of novel hydantoin derivatives: Inhibition of VEGF secretion in liver metastatic osteosarcoma cells.Bioorg. Med. Chem.200917144928493410.1016/j.bmc.2009.06.004 19556138
     [Google Scholar]
  92. Ananda KumarC.S. PrasadS.B.B. VinayaK. ChandrappaS. ThimmegowdaN.R. RanganathaS.R. SwarupS. RangappaK.S. Synthesis and antiproliferative activity of substituted diazaspiro hydantoins: A structure-activity relationship study.Invest. New Drugs200927213113910.1007/s10637‑008‑9150‑3 18607541
     [Google Scholar]
  93. KavithaC.V. NambiarM. NarayanaswamyP.B. ThomasE. RathoreU. Ananda KumarC.S. ChoudharyB. RangappaK.S. RaghavanS.C. Propyl-2-(8-(3,4-difluorobenzyl)-2′,5′-dioxo-8-azaspiro[bicyclo[3.2.1] octane-3,4′-imidazolidine]-1′-yl) acetate induces apoptosis in human leukemia cells through mitochondrial pathway following cell cycle arrest.PLoS One201387e6910310.1371/journal.pone.0069103 23922684
     [Google Scholar]
  94. MichaelidesM.R. KlugeA. PataneM. Van DrieJ.H. WangC. HansenT.M. RisiR.M. ManteiR. HertelC. KarukurichiK. NesterovA. McElligottD. de VriesP. LangstonJ.W. ColeP.A. MarmorsteinR. LiuH. LaskoL. BrombergK.D. LaiA. KesickiE.A. Discovery of spiro oxazolidinediones as selective, orally bioavailable inhibitors of p300/cbp histone acetyltransferases.ACS Med. Chem. Lett.201891283310.1021/acsmedchemlett.7b00395 29348807
     [Google Scholar]
  95. UpadhyayN. TilekarK. LoiodiceF. AnisimovaN.Y. SpirinaT.S. SokolovaD.V. SmirnovaG.B. ChoeJ. Meyer-AlmesF.J. PokrovskyV.S. LavecchiaA. RamaaC.S. Pharmacophore hybridization approach to discover novel pyrazoline-based hydantoin analogs with anti-tumor efficacy.Bioorg. Chem.202110710452710.1016/j.bioorg.2020.104527 33317839
     [Google Scholar]
  96. ŻesławskaE. Kucwaj-BryszK. KincsesA. SpenglerG. SzymańskaE. CzopekA. MarćM.A. KaczorA. NitekW. Domínguez-ÁlvarezE. LataczG. Kieć-KononowiczK. HandzlikJ. An insight into the structure of 5-spiro aromatic derivatives of imidazolidine-2,4-dione, a new group of very potent inhibitors of tumor multidrug resistance in T-lymphoma cells.Bioorg. Chem.202110910473510.1016/j.bioorg.2021.104735 33640632
     [Google Scholar]
  97. ZagórskaA. CzopekA. JarominA. Mielczarek-PutaM. StrugaM. StaryD. BajdaM. Design, synthesis, and in vitro antiproliferative activity of hydantoin and purine derivatives with the 4-acetylphenylpiperazinylalkyl moiety.Materials 20211415415610.3390/ma14154156 34361351
     [Google Scholar]
  98. PengG.W. MarquezV.E. DriscollJ.S. Potential central nervous system antitumor agents. Hydantoin derivatives.J. Med. Chem.197518884684910.1021/jm00242a019 1159704
     [Google Scholar]
  99. BakalovaA. VarbanovH. BuyuklievR. MomekovG. FerdinandovD. KonstantinovS. IvanovD. Synthesis, characterization and biological activity of Pt(II) and Pt(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione.Eur. J. Med. Chem.200843595896510.1016/j.ejmech.2007.06.025 17707952
     [Google Scholar]
  100. BakalovaA. BuyuklievR. VarbanovH. MomekovG. Design, synthesis and comparative cytotoxic investigation of platinum(II) complexes with some derivatives of 5-methyl-5-(4-pyridyl)hydantoin.Inorg. Chim. Acta2014423465110.1016/j.ica.2014.07.030
     [Google Scholar]
  101. LebanJ. BlisseM. KraussB. RathS. BaumgartnerR. SeifertM.H.J. Proteasome inhibition by peptide-semicarbazones.Bioorg. Med. Chem.20081684579458810.1016/j.bmc.2008.02.042 18313310
     [Google Scholar]
  102. KhanfarM.A. AsalB.A. MuditM. KaddoumiA. El SayedK.A. The marine natural-derived inhibitors of glycogen synthase kinase-3β phenylmethylene hydantoins: In vitro and in vivo activities and pharmacophore modeling.Bioorg. Med. Chem.200917166032603910.1016/j.bmc.2009.06.054 19616957
     [Google Scholar]
  103. KhanfarM.A. El SayedK.A. Phenylmethylene hydantoins as prostate cancer invasion and migration inhibitors. CoMFA approach and QSAR analysis.Eur. J. Med. Chem.201045115397540510.1016/j.ejmech.2010.08.066 20869139
     [Google Scholar]
  104. XiaZ. KnaakC. MaJ. BeharryZ.M. McInnesC. WangW. KraftA.S. SmithC.D. Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases.J. Med. Chem.2009521748610.1021/jm800937p 19072652
     [Google Scholar]
  105. ReddyY.T. SekharK.R. SasiN. ReddyP.N. FreemanM.L. CrooksP.A. Novel substituted (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-diones and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones as potent radio-sensitizing agents.Bioorg. Med. Chem. Lett.201020260060210.1016/j.bmcl.2009.11.082 20005706
     [Google Scholar]
  106. Thirupathi ReddyY. Narsimha ReddyP. KoduruS. DamodaranC. CrooksP.A. Aplysinopsin analogs: Synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones.Bioorg. Med. Chem.201018103570357410.1016/j.bmc.2010.03.054 20403701
     [Google Scholar]
  107. MalanconaS. AltamuraS. FilocamoG. KinzelO. HernandoJ.I.M. RowleyM. ScarpelliR. SteinkühlerC. JonesP. Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimid azo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 1.Bioorg. Med. Chem. Lett.201121154422442810.1016/j.bmcl.2011.06.024 21737272
     [Google Scholar]
  108. KinzelO. AlfieriA. AltamuraS. BrunettiM. BufaliS. ColaceciF. FerrignoF. FilocamoG. FonsiM. GallinariP. MalanconaS. HernandoJ.I.M. MonteagudoE. OrsaleM.V. PalumbiM.C. PucciV. RowleyM. SassoR. ScarpelliR. SteinkühlerC. JonesP. Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo- propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 2.Bioorg. Med. Chem. Lett.201121154429443510.1016/j.bmcl.2011.06.023 21737263
     [Google Scholar]
  109. AzizmohammadiM. KhoobiM. RamazaniA. EmamiS. ZarrinA. FiruziO. MiriR. ShafieeA. 2H-chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents.Eur. J. Med. Chem.201359152210.1016/j.ejmech.2012.10.044 23202485
     [Google Scholar]
  110. YamaguchiM. MiyazakiM. KodrasovM.P. RotinsuluH. LosungF. MangindaanR.E.P. de VoogdN.J. YokosawaH. NicholsonB. TsukamotoS. Spongiacidin C, a pyrrole alkaloid from the marine sponge Stylissa massa, functions as a USP7 inhibitor.Bioorg. Med. Chem. Lett.201323133884388610.1016/j.bmcl.2013.04.066 23684893
     [Google Scholar]
  111. YoussefD. ShaalaL. AlshaliK. Bioactive hydantoin alkaloids from the red sea marine sponge Hemimycale arabica.Mar. Drugs201513116609661910.3390/md13116609 26516870
     [Google Scholar]
  112. VitaleR.M. ThellungS. TintoF. SolariA. GattiM. NuzzoG. IoannouE. RoussisV. CiavattaM.L. ManzoE. FlorioT. AmodeoP. Identification of the hydantoin alkaloids parazoanthines as novel CXCR4 antagonists by computational and in vitro functional characterization.Bioorg. Chem.202010510433710.1016/j.bioorg.2020.104337 33113408
     [Google Scholar]
  113. Donnier-MaréchalM. LarchanchéP.E. Le BrocD. FurmanC. CaratoP. MelnykP. Carboline- and phenothiazine-derivated heterocycles as potent SIGMA-1 protein ligands.Eur. J. Med. Chem.20158919820610.1016/j.ejmech.2014.10.053 25462240
     [Google Scholar]
  114. AliW. SpenglerG. KincsesA. NovéM. BattistelliC. LataczG. StarekM. DąbrowskaM. Honkisz-OrzechowskaE. RomanelliA. RasileM.M. SzymańskaE. JacobC. ZwergelC. HandzlikJ. Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma.Eur. J. Med. Chem.202020011243510.1016/j.ejmech.2020.112435 32505850
     [Google Scholar]
  115. DongJ. PanX. YangY. ZhangG. XiaoZ. LiuZ. Design, synthesis and biological evaluation of exiguamine A analogues as IDO1 inhibitors.Eur. J. Med. Chem.202122311363110.1016/j.ejmech.2021.113631 34147748
     [Google Scholar]
  116. ZaskA. BirnbergG. CheungK. KaplanJ. NiuC. NortonE. YamashitaA. BeyerC. KrishnamurthyG. GreenbergerL.M. LoganzoF. Ayral-KaloustianS. D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.Bioorg. Med. Chem. Lett.200414164353435810.1016/j.bmcl.2004.05.005 15261301
     [Google Scholar]
  117. AbdellatifK.R.A. FadalyW.A.A. MostafaY.A. ZaherD.M. OmarH.A. Thiohydantoin derivatives incorporating a pyrazole core: Design, synthesis and biological evaluation as dual inhibitors of topoisomerase-I and cycloxygenase-2 with anti-cancer and anti-inflammatory activities.Bioorg. Chem.20199110313210.1016/j.bioorg.2019.103132 31374529
     [Google Scholar]
  118. Abu AliO.A. Abd El-FattahW. AlfaifiM.Y. ShatiA.A. ElbehairiS.E.I. Abu AlmaatyA.H. ElshaarawyR.F.M. FayadE. New Mn(III)/Fe(III) complexes with thiohydantoin-supported imidazolium ionic liquids for breast cancer therapy.Inorg. Chim. Acta202355112146010.1016/j.ica.2023.121460
     [Google Scholar]
  119. ChangX. ZhangD. QuF. XieY. ChenT. ZhangY. DuQ. BianJ. LiZ. WangJ. XuX. Discovery of thiohydantoin based antagonists of androgen receptor with efficient degradation for the treatment of prostate cancer.Eur. J. Med. Chem.202325711549010.1016/j.ejmech.2023.115490 37209451
     [Google Scholar]
  120. Al-ShawiA.A.A. El-ArabeyA.A. MutlaqD.Z. EltaybW.A. IritiM. AbdallaM. Study on molecular anti-tumor mechanism of 2-Thiohydantoin derivative based on molecular docking and bioinformatic analyses.Curr. Top. Med. Chem.202323644045210.2174/1568026623666230106121527 36617706
     [Google Scholar]
  121. BlancM. CussacM. BoucherleA. LeclercG. Synthesis and immunomodulating activity of 1-amino-2-thiohydantoin derivatives.Eur. J. Med. Chem.199227883984310.1016/0223‑5234(92)90119‑L
     [Google Scholar]
  122. El-ShariefA.M.S. Al-AmriA.M. Al-RaqaS.Y. Halogenated, alkylated and new types of imidazolidine, pyrrolidine, imidazotriazine and thienoimidazole derivatives with biological and antitumor activities.J. Sulfur Chem.200627324526310.1080/17415990600631316
     [Google Scholar]
  123. TranC. OukS. CleggN.J. ChenY. WatsonP.A. AroraV. WongvipatJ. Smith-JonesP.M. YooD. KwonA. WasielewskaT. WelsbieD. ChenC.D. HiganoC.S. BeerT.M. HungD.T. ScherH.I. JungM.E. SawyersC.L. Development of a second-generation antiandrogen for treatment of advanced prostate cancer.Science2009324592878779010.1126/science.1168175 19359544
     [Google Scholar]
  124. NagarajanS. SkoufiasD.A. KozielskiF. PaeA.N. Receptor-ligand interaction-based virtual screening for novel Eg5/kinesin spindle protein inhibitors.J. Med. Chem.20125562561257310.1021/jm201290v 22309208
     [Google Scholar]
  125. MajumdarP. BathulaC. BasuS.M. DasS.K. AgarwalR. HatiS. SinghA. SenS. DasB.B. Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity.Eur. J. Med. Chem.201510254055110.1016/j.ejmech.2015.08.032 26312433
     [Google Scholar]
  126. WuF. JiangH. ZhengB. KogisoM. YaoY. ZhouC. LiX.N. SongY. Inhibition of cancer-associated mutant isocitrate dehydrogenases by 2-thiohydantoin compounds.J. Med. Chem.201558176899690810.1021/acs.jmedchem.5b00684 26280302
     [Google Scholar]
  127. MarianoM. HartmannR.W. EngelM. Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2.Eur. J. Med. Chem.201611220921610.1016/j.ejmech.2016.02.017 26896709
     [Google Scholar]
  128. ElhadyH.A. El-SayedR. Al-nathaliH.S. Design, synthesis and evaluation of anticancer activity of novel 2-thioxoimidazolidin-4-one derivatives bearing pyrazole, triazole and benzoxazole moieties.Chem. Cent. J.20181215110.1186/s13065‑018‑0418‑1 29740713
     [Google Scholar]
  129. ArifI.A. AhamedA. KumarR.S. IdhayadhullaA. ManilalA. Cytotoxic, larvicidal, nematicidal, and antifeedant activities of piperidin-connected 2-thioxoimidazolidin-4-one derivatives.Saudi J. Biol. Sci.201926467368010.1016/j.sjbs.2017.12.007 31048991
     [Google Scholar]
  130. ElbadawiM.M. KhodairA.I. AwadM.K. KassabS.E. ElsaadyM.T. AbdellatifK.R.A. Design, synthesis and biological evaluation of novel thiohydantoin derivatives as antiproliferative agents: A combined experimental and theoretical assessments.J. Mol. Struct.2022124913157410.1016/j.molstruc.2021.131574
     [Google Scholar]
  131. BarrettR.R.G. NashC. DiennetM. Cotnoir-WhiteD. DoyleC. MaderS. ThomsonA.A. GleasonJ.L. Dual-function antiandrogen/HDACi hybrids based on enzalutamide and entinostat.Bioorg. Med. Chem. Lett.20225512844110.1016/j.bmcl.2021.128441 34767912
     [Google Scholar]
  132. NicolescuR.C.B. MaylinZ.R. Pérez-ArealesF.J. IegreJ. PandhaH.S. AsimM. SpringD.R. Hybrid androgen receptor inhibitors Outperform Enzalutamide and EPI‐001 in in vitro models of prostate cancer drug resistance.ChemMedChem2023182e20220054810.1002/cmdc.202200548 36300876
     [Google Scholar]
  133. KimH.R. LeeH.J. ChoiY.J. ParkY.J. WooY. KimS.J. ParkM.H. LeeH.W. ChunP. ChungH.Y. MoonH.R. Benzylidene-linked thiohydantoin derivatives as inhibitors of tyrosinase and melanogenesis: Importance of the β-phenyl-α,β-unsaturated carbonyl functionality.Med. Chem. Commun2014591410141710.1039/C4MD00171K
     [Google Scholar]
  134. EvdokimovN.M. MagedovI.V. McBrayerD. KornienkoA. Isatin derivatives with activity against apoptosis-resistant cancer cells.Bioorg. Med. Chem. Lett.20162661558156010.1016/j.bmcl.2016.02.015 26883150
     [Google Scholar]
  135. XuX. GeR. LiL. WangJ. LuX. XueS. ChenX. LiZ. BianJ. Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents.Eur. J. Med. Chem.20181431325134410.1016/j.ejmech.2017.10.031 29117897
     [Google Scholar]
  136. ChannarP.A. BanoS. HassanS. PerveenF. SaeedA. MahesarP.A. KhanI.A. IqbalJ. Appraisal of novel azomethine–thioxoimidazolidinone conjugates as ecto-5′-nucleotidase inhibitors: Synthesis and molecular docking studies.RSC Adv.20221227175961760610.1039/D2RA02675A 35765454
     [Google Scholar]
  137. Álvarez-PérezM. AliW. MarćM. HandzlikJ. Domínguez-ÁlvarezE. Selenides and Diselenides: A review of their anticancer and chemopreventive activity.Molecules201823362810.3390/molecules23030628 29534447
     [Google Scholar]
  138. RadomskaD. CzarnomysyR. RadomskiD. BielawskiK. Selenium compounds as novel potential anticancer agents.Int. J. Mol. Sci.2021223100910.3390/ijms22031009 33498364
     [Google Scholar]
  139. KoketsuM. TakahashiA. IshiharaH. A facile preparation of selenohydantoins using isoselenocyanate.J. Heterocycl. Chem.2007441798110.1002/jhet.5570440113
     [Google Scholar]
  140. ChennakrishnareddyG. NagendraG. HemanthaH.P. DasU. Guru RowT.N. SureshbabuV.V. Isoselenocyanates derived from Boc/Z-amino acids: Synthesis, isolation, characterization, and application to the efficient synthesis of unsymmetrical selenoureas and selenoureidopeptidomimetics.Tetrahedron201066346718672410.1016/j.tet.2010.06.082
     [Google Scholar]
  141. HemanthaH.P. SureshbabuV.V. Isoselenocyanates derived from amino acid esters: An expedient synthesis and application to the assembly of selenoureidopeptidomimetics, unsymmetrical Selenoureas and selenohydantoins.J. Pept. Sci.2010161164465110.1002/psc.1276 20848599
     [Google Scholar]
  142. GarudD.R. KoketsuM. IshiharaH. Isoselenocyanates: A powerful tool for the synthesis of selenium-containing heterocycles.Molecules200712350453510.3390/12030504 17851407
     [Google Scholar]
  143. IvanenkovY.A. VeselovM.S. RezekinI.G. SkvortsovD.A. SandulenkoY.B. PolyakovaM.V. BezrukovD.S. VasilevskyS.V. KukushkinM.E. MoiseevaA.A. FinkoA.V. KotelianskyV.E. KlyachkoN.L. FilatovaL.A. BeloglazkinaE.K. ZykN.V. MajougaA.G. Synthesis, isomerization and biological activity of novel 2-selenohydantoin derivatives.Bioorg. Med. Chem.201624480281110.1016/j.bmc.2015.12.050 26780833
     [Google Scholar]
  144. ŻesławskaE. KincsesA. UngerV. TóthV. SpenglerG. NitekW. TejchmanW. Exocyclic Sulfur and Selenoorganic compounds towards their anticancer effects: Crystallographic and biological studies.Anticancer Res.20183884577458410.21873/anticanres.12762 30061224
     [Google Scholar]
  145. VyhivskyiO. DlinE.A. FinkoA.V. StepanovaS.P. IvanenkovY.A. SkvortsovD.A. MironovA.V. ZykN.V. MajougaA.G. BeloglazkinaE.K. Copper-promoted C–Se cross-coupling of 2-Selenohydantoins with Arylboronic acids in an open flask.ACS Comb. Sci.201921645646410.1021/acscombsci.9b00021 31009196
     [Google Scholar]
  146. VyhivskyiO. LaikovD.N. FinkoA.V. SkvortsovD.A. ZhirkinaI.V. TafeenkoV.A. ZykN.V. MajougaA.G. BeloglazkinaE.K. Ullmann-type C–Se cross-coupling in the hydantoin family: Synthesis, mechanistic studies, and tests of biological activity.J. Org. Chem.20208553160317310.1021/acs.joc.9b03045 31944122
     [Google Scholar]
  147. KukushkinM. NovotortsevV. FilatovV. IvanenkovY. SkvortsovD. VeselovM. ShafikovR. MoiseevaA. ZykN. MajougaA. BeloglazkinaE. Synthesis and biological evaluation of S-, O- and Se-containing dispirooxindoles.Molecules20212624764510.3390/molecules26247645 34946727
     [Google Scholar]
  148. NovotortsevV.K. KukushkinM.E. TafeenkoV.A. SkvortsovD.A. KalininaM.A. TimoshenkoR.V. ChmelyukN.S. VasilyevaL.A. TarasevichB.N. GorelkinP.V. ErofeevA.S. MajougaA.G. ZykN.V. BeloglazkinaE.K. Dispirooxindoles based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, cytotoxicity and ROS generation ability.Int. J. Mol. Sci.2021225261310.3390/ijms22052613 33807662
     [Google Scholar]
  149. FinkoA.V. SokolovA.I. GukD.A. TafeenkoV.A. MoiseevaA.A. SkvortsovD.A. StomakhinA.A. BeloglazkinA.A. BorisovR.S. PergushovV.I. MelnikovM.Y. ZykN.V. MajougaA.G. BeloglazkinaE.K. Copper coordination compounds with (5 Z, 5 Z ′)-2,2′-(alkane-α,ω-diyldiselenyl)-bis-5-(2-pyridylmethylene)-3,5-dihydro-4-H-imidazol-4-ones. Comparison with sulfur analogue.RSC Adv.202212127133714810.1039/D1RA08995A 35424664
     [Google Scholar]
/content/journals/mrmc/10.2174/0113895575329643241206101210
Loading
Recent Development in Hydantoins, Thiohydantoins, and Selenohydantoins as Anticancer Agents: Structure-activity Relationship and Design Strategies
Mini Rev Med Chem 25, 693 (2025); https://doi.org/10.2174/0113895575329643241206101210
/content/journals/mrmc/10.2174/0113895575329643241206101210
/content/journals/mrmc/10.2174/0113895575329643241206101210
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): 2-selenohydanoin; 2-thiohydantoin; anticancer activity; Hydantoin; hydrogen bond; imidazolidine-2,4-dione

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