Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Topics in Medicinal Chemistry
  4. Volume 25, Issue 1
  5. Article
Volume 25, Issue 1
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Isatin or 1-indole-2,3-dione skeleton has been playing a significant role in drug design and development. Isatin itself and many of its derivatives are widely distributed in naturally occurring bioactive compounds. Various synthetic isatin derivatives were found to possess a broad range of significant pharmacological efficacies especially anti-cancer activity against a wide variety of cancer cell lines. Interestingly, on a few occasions, some isatin-derived scaffolds were reported as more potent than the tested reputed drug molecules. As a result, isatin-derived compounds have been gaining significant attention in cancer-based drug developments. In this review, we have summarized literature reported during the last two decades related to the synthesis of structurally diverse isatin-derived scaffolds with promising anti-cancer activities.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266311332240722065652
2024-08-08
2025-05-10

  • From This Site

    /content/journals/ctmc/10.2174/0115680266311332240722065652
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AyyangarN. LahotiR.J. OtivS.R. Disperse dyes derived by the condensation of homophthalimides and 2-pyridones with naphthostyril and isatin.Dyes Pigments19823431732410.1016/0143‑7208(82)80006‑5
     [Google Scholar]
  2. PremanathanM. RadhakrishnanS. KulangiapparK. SingaraveluG. ThirumalaiarasuV. SivakumarT. KathiresanK. Antioxidant & anticancer activities of isatin (1H-indole-2,3-dione), isolated from the flowers of Couroupita guianensis Aubl.Indian J. Med. Res.2012136582282623287130
     [Google Scholar]
  3. PoppP.D. The chemistry of isatin.Adv. Heterocycl. Chem.19751815810.1016/S0065‑2725(08)60127‑0
     [Google Scholar]
  4. JossangA. JossangP. HadiH.A. SevenetT. BodoB. Horsfiline, an oxindole alkaloid from Horsfieldia superba.J. Org. Chem.199156236527653010.1021/jo00023a016
     [Google Scholar]
  5. EdmondsonS.D. DanishefskyS.J. The total synthesis of spirotryprostatin A.Angew. Chem. Int. Ed.19983781138114010.1002/(SICI)1521‑3773(19980504)37:8<1138::AID‑ANIE1138>3.0.CO;2‑N29711010
     [Google Scholar]
  6. CuiC.B. KakeyaH. OsadaH. Spirotryprostatin B, a novel mammalian cell cycle inhibitor produced by Aspergillus fumigatus.J. Antibiot. (Tokyo)199649883283510.7164/antibiotics.49.8328823522
     [Google Scholar]
  7. LerchnerA. CarreiraE.M. First total synthesis of (+/-)-strychnofoline via a highly selective ring-expansion reaction.J. Am. Chem. Soc.200212450148261482710.1021/ja027906k12475306
     [Google Scholar]
  8. SakiS. AimiN. YamaguchiK. OhhiraH. HoriK. HaginiwaJ. Tetrahedron Lett.19751671571810.1016/S0040‑4039(00)71965‑4
     [Google Scholar]
  9. MaJ. HechtS.M. Javaniside, a novel DNA cleavage agent from Alangium javanicum having an unusual oxindole skeleton.Chem. Commun. (Camb.)20042004101190119110.1039/b402925a15136832
     [Google Scholar]
  10. SharmaA. BanerjeeB. Multicomponent synthesis of isatin-based bioactive heterocycles.Advances in Heterocyclic ChemistryAmsterdamElsevier20242417010.1016/bs.aihch.2023.09.002
     [Google Scholar]
  11. BrandãoP. MarquesC. BurkeA.J. PineiroM. The application of isatin-based multicomponent-reactions in the quest for new bioactive and druglike molecules.Eur. J. Med. Chem.202121111310210.1016/j.ejmech.2020.11310233421712
     [Google Scholar]
  12. Ferraz de PaivaR.E. VieiraE.G. Rodrigues da SilvaD. WegermannC.A. Costa FerreiraA.M. Anticancer compounds based on isatin-derivatives: Strategies to ameliorate selectivity and efficiency.Front. Mol. Biosci.2021762727210.3389/fmolb.2020.62727233614708
     [Google Scholar]
  13. KaurM. KaurM. BandopadhyayT. SharmaA. PriyaA. SinghA. BanerjeeB. Naturally occurring, natural product inspired and synthetic heterocyclic anti-cancer drugs.Phys. Sci. Rev.20238103393344610.1515/psr‑2022‑0003
     [Google Scholar]
  14. PearceS. The importance of heterocyclic compounds in anti-cancer drug design.Drug Discov. World2017186670
     [Google Scholar]
  15. ChowdharyS. Shalini AroraA. KumarV. A mini review on isatin, an anticancer scaffold with potential activities against neglected tropical diseases (NTDs).Pharmaceuticals202215553610.3390/ph1505053635631362
     [Google Scholar]
  16. GideonD.A. AnnaduraiP. NirusimhanV. ParasharA. JamesJ. DhayabaranV.V. Evaluation of the anticancer activities of isatin-based derivatives.Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. ChakrabortiS. SingaporeSpringer202210.1007/978‑981‑16‑1247‑3_51‑1
     [Google Scholar]
  17. WangJ. YunD. YaoJ. FuW. HuangF. ChenL. WeiT. YuC. XuH. ZhouX. HuangY. WuJ. QiuP. LiW. Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds.Eur. J. Med. Chem.201814449350310.1016/j.ejmech.2017.12.04329288946
     [Google Scholar]
  18. SakamotoK.M. Semaxanib (SUGEN).IDrugs2001491061106715965852
     [Google Scholar]
  19. KudoM. ChengA.L. ParkJ.W. ParkJ.H. LiangP.C. HidakaH. IzumiN. HeoJ. LeeY.J. SheenI.S. ChiuC.F. AriokaH. MoritaS. AraiY. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): A randomised, double-blind, placebo-controlled, multicentre, phase 3 study.Lancet Gastroenterol. Hepatol.201831374610.1016/S2468‑1253(17)30290‑X28988687
     [Google Scholar]
  20. RiniB.I. Sunitinib.Expert Opin. Pharmacother.20078142359236910.1517/14656566.8.14.235917927489
     [Google Scholar]
  21. LondonC. MathieT. StingleN. CliffordC. HaneyS. KleinM.K. BeaverL. VickeryK. VailD.M. HersheyB. EttingerS. VaughanA. AlvarezF. HillmanL. KiselowM. ThammD. HigginbothamM.L. GauthierM. KrickE. PhillipsB. LaDueT. JonesP. BryanJ. GillV. NovasadA. FultonL. CarrerasJ. McNeillC. HenryC. GillingsS. Preliminary evidence for biologic activity of toceranib phosphate (Palladia ® ) in solid tumours.Vet. Comp. Oncol.201210319420510.1111/j.1476‑5829.2011.00275.x22236194
     [Google Scholar]
  22. KaurM. PriyaA. SharmaA. SinghA. BanerjeeB. Glycine and its derivatives catalyzed one-pot multicomponent synthesis of bioactive heterocycles.Synth. Commun.202252161635165610.1080/00397911.2022.2090262
     [Google Scholar]
  23. PriyaA. SharmaA. KaurM. SinghA. BanerjeeB. Preyssler catalyst: A heterogeneous polyacidic catalyst for the efficient synthesis of diverse bioactive heterocyclic scaffolds.ARKIVOC2022202238511110.24820/ark.5550190.p011.783
     [Google Scholar]
  24. BanerjeeB. SinghA. KaurG. Baker’s yeast ( Saccharomyces cerevisiae ) catalyzed synthesis of bioactive heterocycles and some stereoselective reactions.Phys. Sci. Rev.202274-530132310.1515/psr‑2021‑0021
     [Google Scholar]
  25. SharmaA. PriyaA. KaurM. SinghA. KaurG. BanerjeeB. Ultrasound-assisted synthesis of bioactive S -heterocycles.Synth. Commun.202151213209323610.1080/00397911.2021.1970775
     [Google Scholar]
  26. BanerjeeB. KaurG. KaurN. p-Sulfonic acid calix[n]arene catalyzed synthesis of bioactive heterocycles: A review.Curr. Org. Chem.202125120922210.2174/1385272824999201019162655
     [Google Scholar]
  27. BanikB.K. BanerjeeB. KaurG. SarochS. KumarR. Tetrabutylammonium bromide (TBAB) catalyzed synthesis of bioactive heterocycles.Molecules20202524591810.3390/molecules2524591833327504
     [Google Scholar]
  28. BanerjeeB. KaurG. Microwave assisted catalyst-free synthesis of bioactive heterocycles.Curr. Microw. Chem.20207152210.2174/2213335607666200226102010
     [Google Scholar]
  29. KaurG. SinghA. BalaK. DeviM. KumariA. DeviS. DeviR. GuptaV.K. BanerjeeB. Naturally occurring organic acid-catalyzed facile diastereoselective synthesis of biologically active (E)-3-(arylimino)indolin-2-one derivatives in water at room temperature.Curr. Org. Chem.201923161778178810.2174/1385272822666190924182538
     [Google Scholar]
  30. KaurG. BalaK. DeviS. BanerjeeB. Camphorsulfonic Acid (CSA): An efficient organocatalyst for the synthesis or derivatization of heterocycles with biologically promising activities.Curr. Green Chem.20185315016710.2174/2213346105666181001113413
     [Google Scholar]
  31. KaurG. DeviP. ThakurS. KumarA. ChandelR. BanerjeeB. Magnetically separable transition metal ferrites: Versatile heterogeneous nano-catalysts for the synthesis of diverse bioactive heterocycles.ChemistrySelect2019472181219910.1002/slct.201803600
     [Google Scholar]
  32. SinghP. KaurS. KumarV. BediP.M.S. MahajanM.P. SeharI. PalH.C. SaxenaA.K. Synthesis and in vitro cytotoxic evaluation of N-alkylbromo and N-alkylphthalimido-isatins.Bioorg. Med. Chem. Lett.201121103017302010.1016/j.bmcl.2011.03.04321482109
     [Google Scholar]
  33. LvK. WangL.L. LiuM.L. ZhouX.B. FanS.Y. LiuH.Y. ZhengZ.B. LiS. Synthesis and antitumor activity of 5-[1-(3-(dimethylamino)propyl)-5-halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxamides.Bioorg. Med. Chem. Lett.201121103062306510.1016/j.bmcl.2011.03.03121450463
     [Google Scholar]
  34. MatesicL. LockeJ.M. BremnerJ.B. PyneS.G. SkropetaD. RansonM. VineK.L. N-Phenethyl and N-naphthylmethyl isatins and analogues as in vitro cytotoxic agents.Bioorg. Med. Chem.20081663118312410.1016/j.bmc.2007.12.02618182300
     [Google Scholar]
  35. ChoiS.J. LeeJ.E. JeongS.Y. ImI. LeeS.D. LeeE.J. LeeS.K. KwonS.M. AhnS.G. YoonJ.H. HanS.Y. KimJ.I. KimY.C. 5,5′-substituted indirubin-3′-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity.J. Med. Chem.20105393696370610.1021/jm100080z20361800
     [Google Scholar]
  36. ModiN.R. ShahR.J. PatelM.J. SutharM. ChauhanB.F. PatelL.J. Design, synthesis, and QSAR study of novel 2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-N-phenylacetamide derivatives as cytotoxic agents.Med. Chem. Res.201120561562510.1007/s00044‑010‑9361‑y
     [Google Scholar]
  37. HanK. ZhouY. LiuF. GuoQ. WangP. YangY. SongB. LiuW. YaoQ. TengY. YuP. Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents.Bioorg. Med. Chem. Lett.201424259159410.1016/j.bmcl.2013.12.00124360564
     [Google Scholar]
  38. SinghP. SharmaP. AnandA. BediP.M.S. KaurT. SaxenaA.K. KumarV. Azide-alkyne cycloaddition en route to novel 1H-1,2,3-triazole tethered isatin conjugates with in vitro cytotoxic evaluation.Eur. J. Med. Chem.20125545546110.1016/j.ejmech.2012.06.05722818042
     [Google Scholar]
  39. HavrylyukD. KovachN. ZimenkovskyB. VasylenkoO. LesykR. Synthesis and anticancer activity of isatin-based pyrazolines and thiazolidines conjugates.Arch. Pharm. (Weinheim)2011344851452210.1002/ardp.20110005521681810
     [Google Scholar]
  40. MaliP.R. ShirsatP.K. KhomaneN. NayakL. NanuboluJ.B. MeshramH.M. 1,3-Dipolar cycloaddition reactions for the synthesis of novel oxindole derivatives and their cytotoxic properties.ACS Comb. Sci.2017191063363910.1021/acscombsci.7b0004428816439
     [Google Scholar]
  41. KamalA. BabuK.S. Vishnu VardhanM.V.P.S. HussainiS.M.A. MaheshR. ShaikS.P. AlarifiA. Sulfamic acid promoted one-pot three-component synthesis and cytotoxic evaluation of spirooxindoles.Bioorg. Med. Chem. Lett.201525102199220210.1016/j.bmcl.2015.03.05425870131
     [Google Scholar]
  42. KumarR.S. AlmansourA.I. ArumugamN. MohammadF. KotreshaD. MenéndezJ.C. Spirooxindole-pyrrolidine heterocyclic hybrids promotes apoptosis through activation of caspase-3.Bioorg. Med. Chem.201927122487249810.1016/j.bmc.2019.03.01130853330
     [Google Scholar]
  43. TanW. ZhuX.T. ZhangS. XingG.J. ZhuR.Y. ShiF. Diversity-oriented synthesis of spiro-oxindole-based 2,5-dihydropyrroles via three-component cycloadditions and evaluation on their cytotoxicity.RSC Advances2013327108751088610.1039/c3ra40874d
     [Google Scholar]
  44. BarakatA. IslamM.S. GhawasH.M. Al-MajidA.M. El-SendunyF.F. BadriaF.A. ElshaierY.A.M.M. GhabbourH.A. Substituted spirooxindole derivatives as potent anticancer agents through inhibition of phosphodiesterase 1.RSC Advances2018826143351434610.1039/C8RA02358A35540737
     [Google Scholar]
  45. LiuX-L. YangC. ZhangW.H. ZhouG. MaX.T. LinB. ZhangM. ZhouY. FengT.T. Construction of turmerone motif-fused spiropyrrolidine oxindoles and their biological evaluation for anticancer activities.Tetrahedron Lett.201657121385138910.1016/j.tetlet.2016.02.074
     [Google Scholar]
  46. Al-MajidA.M. GhawasH.M. IslamM.S. SolimanS.M. El-SendunyF.F. BadriaF.A. AliM. ShaikM.R. GhabbourH.A. BarakatA. Synthesis of spiroindolone analogue via three components reaction of olefin with isatin and sarcosine: Anti proliferative activity and computational studies.J. Mol. Struct.2020120412750010.1016/j.molstruc.2019.127500
     [Google Scholar]
  47. MaddelaS. MakulaA. GalignianaM.D. ParambiD.G.T. FedericciF. MazairaG. HendawyO.M. DevS. MathewG.E. MathewB. Fe3O4 nanoparticles mediated synthesis of novel spirooxindole-dihydropyrimidinone molecules as Hsp90 inhibitors.Arch. Pharm.20193521800174
     [Google Scholar]
  48. WuL. LiuY. LiY. Synthesis of spirooxindole-O-naphthoquinone-tetrazolo[1,5-a]pyrimidine hybrids as potential anticancer agents.Molecules2018239233010.3390/molecules2309233030213123
     [Google Scholar]
  49. ZhangY.L. LiY.F. WangJ.W. YuB. ShiY.K. LiuH.M. Multicomponent assembly of novel antiproliferative steroidal dihydropyridinyl spirooxindoles.Steroids2016109222810.1016/j.steroids.2016.03.00526976211
     [Google Scholar]
  50. ArunY. BhaskarG. BalachandranC. IgnacimuthuS. PerumalP.T. Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line.Bioorg. Med. Chem. Lett.20132361839184510.1016/j.bmcl.2013.01.02323395665
     [Google Scholar]
  51. DongH. SongS. LiJ. XuC. ZhangH. OuyangL. The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation.Bioorg. Med. Chem. Lett.201525173585359110.1016/j.bmcl.2015.06.07626159483
     [Google Scholar]
  52. LinB. ZhangW.H. WangD.D. GongY. WeiQ.D. LiuX.L. FengT.T. ZhouY. YuanW.C. 3-Methyl-4-nitro-5-isatylidenyl-isoxazoles as 1,3-dipolarophiles for synthesis of polycyclic 3,3′-pyrrolidinyl-dispirooxindoles and their biological evaluation for anticancer activities.Tetrahedron201773345176518810.1016/j.tet.2017.07.011
     [Google Scholar]
  53. ShyamsivappanS. VivekR. SaravananA. ArasakumarT. SubashiniG. SureshT. ShankarR. MohanP.S. Synthesis and X-ray study of dispiro 8-nitroquinolone analogues and their cytotoxic properties against human cervical cancer HeLa cells.MedChemComm201910343944910.1039/C8MD00482J31015907
     [Google Scholar]
  54. ChavanP.V. DesaiU.V. WadgaonkarP.P. TapaseS.R. KodamK.M. ChoudhariA. SarkarD. Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents.Bioorg. Chem.20198547548610.1016/j.bioorg.2019.01.07030776558
     [Google Scholar]
  55. ParthasarathyK. PraveenC. BalachandranC. Senthil kumarP. IgnacimuthuS. PerumalP.T. Cu(OTf)2 catalyzed three component reaction: Efficient synthesis of spiro[indoline-3,4′-pyrano[3,2-b]pyran derivatives and their anticancer potency towards A549 human lung cancer cell lines.Bioorg. Med. Chem. Lett.20132392708271310.1016/j.bmcl.2013.02.08623522833
     [Google Scholar]
  56. PatravaleA.A. GoreA.H. KolekarG.B. DeshmukhM.B. ChoudhariP.B. BhatiaM.S. PrabhuS. JamdhadeM.D. PatoleM.S. AnbhuleP.V. Synthesis, biological evaluation and molecular docking studies of some novel indenospiro derivatives as anticancer agents.J. Taiwan Inst. Chem. Eng.20166810511810.1016/j.jtice.2016.09.034
     [Google Scholar]
  57. KidwaiM. JainA. NemayshV. KumarR. LuthraP.M. Efficient entry to diversely functionalized spirooxindoles from isatin and their biological activity.Med. Chem. Res.20132262717272310.1007/s00044‑012‑0249‑x
     [Google Scholar]
  58. WangD.C. FanC. XieY.M. YaoS. SongH. Efficient and mild one-pot synthesis of (E)-8′-arylidene-5′,6′,7′,8′-tetrahydrospiro[oxindole-3,4′-pyrano[3,2-c]pyridin] derivatives with potential antitumor activity.Arab. J. Chem.20191281918192410.1016/j.arabjc.2014.12.003
     [Google Scholar]
  59. KumarM.R. ManikandanA. SivakumarA. DhayabaranV.V. An eco-friendly catalytic system for multicomponent, one-pot synthesis of novel spiro-chromeno indoline-triones and their anti-prostate cancer potentials evaluated via alkaline phosphatase inhibition mechanism.Bioorg. Chem.201881445410.1016/j.bioorg.2018.07.03730118985
     [Google Scholar]
  60. NagarajuB. KovvuriJ. BabuK.S. AdiyalaP.R. NayakV.L. AlarifiA. KamalA. A facile one pot C C and C N bond formation for the synthesis of spiro-benzodiazepines and their cytotoxicity.Tetrahedron201773496969697610.1016/j.tet.2017.10.060
     [Google Scholar]
  61. El-NaggarM. EldehnaW.M. AlmahliH. ElgezA. FaresM. ElaasserM.M. Abdel-AzizH.A. Novel Thiazolidinone/Thiazolo[3,2-a] benzimidazolone-isatin conjugates as apoptotic anti-proliferative agents towards breast cancer: One-pot synthesis and in vitro biological evaluation.Molecules2018236142010.3390/molecules2306142029895744
     [Google Scholar]
  62. MeledduR. PetrikaiteV. DistintoS. ArriduA. AngiusR. SerusiL. ŠkarnulytėL. EndriulaitytėU. Paškevičiu̅tėM. CottigliaF. GaspariM. TavernaD. DeplanoS. FoisB. MaccioniE. Investigating the anticancer activity of isatin/dihydropyrazole hybrids.ACS Med. Chem. Lett.201910457157610.1021/acsmedchemlett.8b0059630996798
     [Google Scholar]
  63. SolomonV.R. HuC. LeeH. Hybrid pharmacophore design and synthesis of isatin–benzothiazole analogs for their anti-breast cancer activity.Bioorg. Med. Chem.200917217585759210.1016/j.bmc.2009.08.06819804979
     [Google Scholar]
  64. IslamM.S. GhawasH.M. El-SendunyF.F. Al-MajidA.M. ElshaierY.A.M.M. BadriaF.A. BarakatA. Synthesis of new thiazolo-pyrrolidine–(spirooxindole) tethered to 3-acylindole as anticancer agents.Bioorg. Chem.20198242343010.1016/j.bioorg.2018.10.03630508794
     [Google Scholar]
  65. ArunY. SaranrajK. BalachandranC. PerumalP.T. Novel spirooxindole–pyrrolidine compounds: Synthesis, anticancer and molecular docking studies.Eur. J. Med. Chem.201474506410.1016/j.ejmech.2013.12.02724445312
     [Google Scholar]
  66. KumarA. GuptaG. SrivastavaS. BishnoiA.K. SaxenaR. KantR. KhannaR.S. MaulikP.R. DwivediA. Novel diastereoselective synthesis of spiropyrrolidine-oxindole derivatives as anti-breast cancer agents.RSC Advances20133144731473510.1039/c3ra21595d
     [Google Scholar]
  67. KaminskyyD. KhylukD. VasylenkoO. ZaprutkoL. LesykR. A facile synthesis and anticancer activity evaluation of spiro[thiazolidinone-isatin] conjugates.Sci. Pharm.201179476377710.3797/scipharm.1109‑1422145104
     [Google Scholar]
  68. LiuX.W. YaoZ. YangJ. ChenZ.Y. LiuX.L. ZhaoZ. LuY. ZhouY. CaoY. 1,3-Dipolar cycloaddition enabled isoxazole-fused spiropyrrolidine oxindoles syntheses from 3-methyl-4-nitro-5-alkenyl-isoxazoles and azomethine ylides.Tetrahedron201672101364137410.1016/j.tet.2016.01.029
     [Google Scholar]
  69. LotfyG. SaidM.M. Synthesis of new spirooxindole-pyrrolothiazoles derivatives: Anti-cancer activity and molecular docking.Bioorg. Med. Chem.2017251514152310.1016/j.bmc.2017.01.01428126436
     [Google Scholar]
/content/journals/ctmc/10.2174/0115680266311332240722065652
Loading
Synthesis of Isatin-derived Heterocycles with Promising Anticancer Activities
Curr. Top. Med. Chem. 25, 96 (2025); https://doi.org/10.2174/0115680266311332240722065652
/content/journals/ctmc/10.2174/0115680266311332240722065652
/content/journals/ctmc/10.2174/0115680266311332240722065652
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Anti-cancer; Anti-proliferative; Anti-tumor; Cytotoxicity; Functionalized isatins; Isatin; Isatin-derived heterocycles

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