Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Organic Synthesis
  4. Volume 22, Issue 3
  5. Article
Volume 22, Issue 3
  • ISSN: 1570-1794
  • E-ISSN: 1875-6271

Abstract

Indolizidine alkaloids represent a diverse group of naturally occurring compounds which are derived from various sources and possess a wide range of pharmacological activities. Fused indolizidine alkaloids represent a distinct subset of these compounds, where additional rings are fused with the indolizidine core. When combined with the specific stereochemistry typically required for their biological activity, the fused ring structure complicates the synthesis of this important class of compounds. Among the well-studied fused indolizidine alkaloids are securinine, gephyrotoxin, and lepadiformine, which have all exhibited potential in important therapeutic areas. Due to their complex structures, over the years numerous approaches have been proposed to synthesize these compounds. In this article, we review the progress made in synthetic routes for these key fused indolizidine alkaloids throughout history, providing a broad overview and the distinct advantages of the various strategies that could be employed in their synthesis.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cos/10.2174/0115701794332632240918043021
2024-10-02
2025-05-11

  • From This Site

    /content/journals/cos/10.2174/0115701794332632240918043021
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. ZhangJ. Morris-NatschkeS.L. MaD. ShangX.F. YangC.J. LiuY.Q. LeeK.H. Biologically active indolizidine alkaloids.Med. Res. Rev.202141292896010.1002/med.2174733128409
     [Google Scholar]
  2. TakahataH. Takefumi MomoseA.N.D. Simple indolizidine alkaloids.The alkaloids.Academic Press, Inc.199744189256
     [Google Scholar]
  3. MichaelJ.P. Indolizidine and quinolizidine alkaloids.Nat. Prod. Rep.200522560362610.1039/b413748p16193159
     [Google Scholar]
  4. RatmanovaN.K. AndreevI.A. LeontievA.V. MomotovaD. NovoselovA.M. IvanovaO.A. TrushkovI.V. Strategic approaches to the synthesis of pyrrolizidine and indolizidine alkaloids.Tetrahedron2020761413103110.1016/j.tet.2020.131031
     [Google Scholar]
  5. XieL. LiangS. JiwaH. ZhangL. LuQ. WangX. LuoL. XiaH. LiZ. WangJ. LuoX. LuoJ. Securinine inhibits the tumor growth of human bladder cancer cells by suppressing Wnt/β-catenin signaling pathway and activating p38 and JNK signaling pathways.Biochem. Pharmacol.202422311612510.1016/j.bcp.2024.11612538484850
     [Google Scholar]
  6. LeonoudakisD. RaneA. AngeliS. LithgowG.J. AndersenJ.K. ChintaS.J. Anti-inflammatory and neuroprotective role of natural product securinine in activated glial cells: Implications for Parkinson’s Disease.Mediators Inflamm.2017201711110.1155/2017/830263628473732
     [Google Scholar]
  7. XiaoH. ZhangQ. ZhongP. TangG. TaoL. HuangZ. GuoD. LiaoY. PengY. WuZ.L. WangY. YeW.C. ShiL. Securinine promotes neuronal development and exhibits antidepressant-like effects via mTOR activation.ACS Chem. Neurosci.202112193650366110.1021/acschemneuro.1c0038134541857
     [Google Scholar]
  8. TangG. LiuX. MaN. HuangX. WuZ.L. ZhangW. WangY. ZhaoB.X. WangZ.Y. IpF.C.F. IpN.Y. YeW.C. ShiL. ChenW.M. Design and synthesis of dimeric securinine analogues with neuritogenic activities.ACS Chem. Neurosci.20167101442145110.1021/acschemneuro.6b0018827467236
     [Google Scholar]
  9. GuptaK. ChakrabartiA. RanaS. RamdeoR. RothB.L. AgarwalM.L. TseW. AgarwalM.K. WaldD.N. Securinine, a myeloid differentiation agent with therapeutic potential for AML.PLoS One201166e2120310.1371/journal.pone.002120321731671
     [Google Scholar]
  10. HanS. ZhangG. LiM. ChenD. WangY. YeW. JiZ. L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway.Oncol. Rep.20143152245225110.3892/or.2014.310124676995
     [Google Scholar]
  11. FriessS. DurantR.C. WhitcombE.R. ReberL.J. ThommesenW.C. Some toxicologic properties of the alkaloids galanthamine and securinine*1.Toxicol. Appl. Pharmacol.19613334735710.1016/0041‑008X(61)90071‑013702084
     [Google Scholar]
  12. LiuC.J. FanX.D. JiangJ.G. ChenQ.X. ZhuW. Potential anticancer activities of securinine and its molecular targets.Phytomedicine202210615441710.1016/j.phymed.2022.15441736063584
     [Google Scholar]
  13. RajputA SharmaR BhartiR Pharmacological activities and toxicities of alkaloids on human health.Mater Today Proc20214851407141510.1016/j.matpr.2021.09.189
     [Google Scholar]
  14. DalyJ.W. Biologically active alkaloids from poison frogs (Dendrobatidae).J. Toxicol. Toxin Rev.198211338610.3109/155695482090164677049875
     [Google Scholar]
  15. JohnsonA. A stereodivergent synthesis of the anti-inflammatory agent BIRT-377. Approaches to the synthesis of gephyrotoxin.Master's thesis, University of Calgary, Calgary, Canada201410.11575/PRISM/25038
     [Google Scholar]
  16. DalyJ.W. WitkopB. TokuyamaT. NishikawaT. KarleI.L. WashingtonD.C. Gephyrotoxins, histrionicotoxins and pumiliotoxins from the neotropical frog Dendrobates histrionicus.Helv. Chim. Acta19776031128114010.1002/hlca.19770600336863724
     [Google Scholar]
  17. AronstamR.S. DalyJ.W. SpandeT.F. NarayananT.K. AlbuquerqueE.X. Interaction of gephyrotoxin and indolizidine alkaloids with the nicotinic acetylcholine receptorion channel complex of torpedo electroplax.Neurochem. Res.19861181227124010.1007/BF009659502431336
     [Google Scholar]
  18. HabermehlG.G. Antimicrobial activity of amphibian venoms.Stud. Nat. Prod. Chem.19951532733910.1016/S1572‑5995(06)80135‑3
     [Google Scholar]
  19. MayerA.M.S. HamannM.T. Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action.Comp. Biochem. Physiol. C Toxicol. Pharmacol.20051403-426528610.1016/j.cca.2005.04.00415919242
     [Google Scholar]
  20. JugéM. GrimaudN. BiardJ.F. SauviatM.P. NabilM. VerbistJ.F. PetitJ.Y. Cardiovascular effects of lepadiformine, an alkaloid isolated from the ascidians Clavelina lepadiformis (Müller) and C. moluccensis (Sluiter).Toxicon20013981231123710.1016/S0041‑0101(01)00079‑411306135
     [Google Scholar]
  21. SongQ. LiuY. CaiL. CaoX. QianS. WangZ. One-pot tandem route to fused indolizidines and quinolizidines: Application in the synthesis of alkaloids and bioactive compounds.Chin. Chem. Lett.20213251713171610.1016/j.cclet.2021.01.018
     [Google Scholar]
  22. BlancoM.J. SardinaF.J. Enantiospecific and stereoselective synthesis of polyhydroxylated pyrrolidines and indolizidines from trans-4-hydroxy-L-proline.J. Org. Chem.199661144748475510.1021/jo960424511667406
     [Google Scholar]
  23. MassicotF. MessireG. ValléeA. VasseJ.L. PyS. BehrJ.B. Regiospecific formation of sugar-derived ketonitrone towards unconventional C -branched pyrrolizidines and indolizidines.Org. Biomol. Chem.201917297066707710.1039/C9OB01419E31298253
     [Google Scholar]
  24. SeiglerD. 30 Pyrrolizidine, quinolizidine, and indolizidine alkaloids.Plant secondary metabolism.New YorkSpringer Boston MA199854654710.1007/978‑1‑4615‑4913‑0_30
     [Google Scholar]
  25. MichaelJ.P. Simple indolizidine and quinolizidine alkaloids.The alkaloids.Academic Press, Inc.2001559125810.1016/S0099‑9598(01)55004‑X
     [Google Scholar]
  26. BhatC. TilveS.G. Recent advances in the synthesis of naturally occurring pyrrolidines, pyrrolizidines and indolizidine alkaloids using proline as a unique chiral synthon.RSC Advances20144115405545210.1039/c3ra44193h
     [Google Scholar]
  27. SalunkeR.V. RameshN.G. Divergent synthesis of amino-substituted indolizidine alkaloids, decahydropyrazino[2,1,6-cd]pyrrolizine triols, and (–)-pochonicine stereoisomers.Eur. J. Org. Chem.20202020172626264010.1002/ejoc.202000194
     [Google Scholar]
  28. WagnerS. SiglS. SchenklM. BreuningM. Diastereodivergent synthesis of the quinolizidine-indolizidine alkaloids of the leontidine/camoensine family.Eur. J. Org. Chem.20212021172498250510.1002/ejoc.202100270
     [Google Scholar]
  29. ParkS. KangG. KimC. KimD. HanS. Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core.Nat. Commun.2022131514910.1038/s41467‑022‑32902‑z36056139
     [Google Scholar]
  30. HondaT. NamikiH. KanedaK. MizutaniH. First diastereoselective chiral synthesis of (-)-securinine.Org. Lett.200461878910.1021/ol036125114703357
     [Google Scholar]
  31. PerezM. AyadT. MaillosP. PoughonV. FahyJ. Ratovelomanana-VidalV. Synthesis and antiproliferative and metabolic evaluations of novel securinine derivatives.ACS Med. Chem. Lett.20167440340710.1021/acsmedchemlett.5b0044127096049
     [Google Scholar]
  32. AlibésR. BallbéM. BusquéF. de MarchP. EliasL. FigueredoM. FontJ. A new general access to either type of Securinega alkaloids: synthesis of securinine and (-)-allonorsecurinine.Org. Lett.20046111813181610.1021/ol049455+15151421
     [Google Scholar]
  33. González-GálvezD. García-GarcíaE. AlibésR. BayónP. de MarchP. FigueredoM. FontJ. Enantioselective approach to Securinega alkaloids. Total synthesis of securinine and (-)-norsecurinine.J. Org. Chem.200974166199621110.1021/jo901059n19627163
     [Google Scholar]
  34. WehlauchR. GademannK. Securinega alkaloids: Complex structures, potent bioactivities, and efficient total syntheses.Asian J. Org. Chem.2017691146115910.1002/ajoc.201700142
     [Google Scholar]
  35. ZhangJ. YaoJ. PengS. LiX. FangJ. Securinine disturbs redox homeostasis and elicits oxidative stress-mediated apoptosis via targeting thioredoxin reductase.Biochim. Biophys. Acta Mol. Basis Dis.20171863112913810.1016/j.bbadis.2016.10.01927777067
     [Google Scholar]
  36. BeutlerJ.A. KarbonE.W. BrubakerA.N. MalikR. CurtisD.R. EnnaS.J. Securinine alkaloids: A new class of GABA receptor antagonist.Brain Res.1985330113514010.1016/0006‑8993(85)90014‑92985189
     [Google Scholar]
  37. ZhengX. LiuJ. YeC.X. WangA. WangA.E. HuangP.Q. SmI2-mediated radical coupling strategy to Securinega alkaloids: Total synthesis of (-)-14,15-dihydrosecurinine and formal total synthesis of (-)-securinine.J. Org. Chem.20158021034104110.1021/jo502522x25496326
     [Google Scholar]
  38. MensahJ.L. LagardeI. CeschinC. MichelbG. GleyeJ. FourasteI. Antibacterial activity of the leaves of Phyllanthus discoideus.J. Ethnopharmacol.199028112913310.1016/0378‑8741(90)90069‑62156112
     [Google Scholar]
  39. RanaS. GuptaK. GomezJ. MatsuyamaS. ChakrabartiA. AgarwalM.L. AgarwalA. AgarwalM.K. WaldD.N. Securinine induces p73‐dependent apoptosis preferentially in p53‐deficient colon cancer cells.FASEB J.20102462126213410.1096/fj.09‑14899920133503
     [Google Scholar]
  40. HoriiZ. HanaokaM. YamawakiY. TamuraY. SaitoS. ShigematsuN. KoteraK. YoshikawaH. SatoY. NakaiH. SugimotoN. The total synthesis of securinine and virosecurinine.Tetrahedron19672331165117410.1016/0040‑4020(67)85066‑X
     [Google Scholar]
  41. LirasS. DavorenJ.E. BordnerJ. An approach to the skeleton of the securinega alkaloids. The total synthesis of (+/-)-securinine.Org. Lett.20013570370610.1021/ol007048211259041
     [Google Scholar]
  42. DhudshiaB. CooperB.F.T. MacdonaldC.L.B. ThadaniA.N. The asymmetric total synthesis of (−)-securinine.Chem. Commun.20094446346510.1039/B816576A19137186
     [Google Scholar]
  43. PiccichèM. PintoA. GrieraR. BoschJ. AmatM. Enantioselective total synthesis of (+)-gephyrotoxin 287C.Org. Lett.201719246654665710.1021/acs.orglett.7b0338129182285
     [Google Scholar]
  44. Mensah-DwumahM. DalyJ.W. Pharmacological activity of alkaloids from poison-dart frogs (dendrobatidae).Toxicon197816218919410.1016/0041‑0101(78)90037‑5635932
     [Google Scholar]
  45. SmithC.J. HolmesA.B. PressN.J. The total synthesis of alkaloids (–)-histrionicotoxin 259A, 285C and 285EAll new compounds exhibited satisfactory spectroscopic and analytical and/or exact mass data. Electronic supplementary information (ESI) available: experimental procedures for the preparation of compounds 4, 5, 13, 16, 22 and 25. See http://www.rsc.org/suppdata/cc/b1/b111514f/.Chem. Commun.20022111214121510.1039/b111514f12109088
     [Google Scholar]
  46. MatsumuraK. NishikawaK. YoshidaH. DoeM. MorimotoY. Formal total synthesis of histrionicotoxin alkaloids via Hg(OTf) 2 -catalyzed cycloisomerization and SmI 2 -induced ring expansion.RSC Advances2018821112961130310.1039/C8RA02011F35542821
     [Google Scholar]
  47. ShabirG. SaeedA. AliF. A comparative study of synthetic approaches towards total synthesis of histrionicotoxin: A selective inhibitor of nicotinic acetylcholine receptors.J. Asian Nat. Prod. Res.2021231091993710.1080/10286020.2020.181067032835524
     [Google Scholar]
  48. FujimotoR. KishiY. BlountJ.F. Total synthesis of (.+-.)-gephyrotoxin.J. Am. Chem. Soc.1980102237154715610.1021/ja00543a067
     [Google Scholar]
  49. FujimotoR. KishiY. On the absolute configuration of gephyrotoxin.Tetrahedron Lett.198122424197419810.1016/S0040‑4039(01)82102‑X
     [Google Scholar]
  50. OvermanL.E. LesuisseD. HashimotoM. Synthetic applications of N-acylamino-1,3-dienes. 10. Importance of allylic interactions and stereoelectronic effects in dictating the steric course of the reaction of iminium ions with nucleophiles. An efficient total synthesis of (.+-.)-gephyrotoxin.J. Am. Chem. Soc.1983105165373537910.1021/ja00354a031
     [Google Scholar]
  51. OvermanLE FukayaC Stereoselective total synthesis of perhydrogephyrotoxin. Synthetic applications of directed 2-azonia-[3,3]-sigmatropic rearrangements.J Am Chem Soc198010241454145610.1021/ja00524a057
     [Google Scholar]
  52. HartD.J. KanaiK. Total syntheses of dl-gephyrotoxin and dl-dihydrogephyrotoxin.J. Am. Chem. Soc.198310551255126310.1021/ja00343a030
     [Google Scholar]
  53. ItoY. NakajoE. NakatsukaM. SaegusaT. A new approach to gephyrotoxin.Tetrahedron Lett.198324282881288410.1016/S0040‑4039(00)88049‑1
     [Google Scholar]
  54. WeiL.L. HsungR.P. SklenickaH.M. GerasyutoA.I. Gerasyuto AI. A novel and highly stereoselective intramolecular formal [3+3] cycloaddition reaction of vinylogous amides tethered with α,β-unsaturated aldehydes: A formal total synthesis of (+)-gephyrotoxin.Angew. Chem.200111381564156610.1002/1521‑3757(20010417)113:8<1564::AID‑ANGE1564>3.0.CO;2‑J
     [Google Scholar]
  55. ShirokaneK. WadaT. YoritateM. MinamikawaR. TakayamaN. SatoT. ChidaN. Total synthesis of (±)-gephyrotoxin by amide-selective reductive nucleophilic addition.Angew. Chem. Int. Ed.201453251251610.1002/anie.20130890524288230
     [Google Scholar]
  56. SatoT. YoritateM. TajimaH. ChidaN. Total synthesis of complex alkaloids by nucleophilic addition to amides.Org. Biomol. Chem.201816213864387510.1039/C8OB00733K29701231
     [Google Scholar]
  57. ChuS. WallaceS. SmithM.D. A cascade strategy enables a total synthesis of (-)-gephyrotoxin.Angew. Chem. Int. Ed.20145350138261382910.1002/anie.20140903825324224
     [Google Scholar]
  58. ToyookaN. TakashimaK. Formal synthesis of gephyrotoxin 287C.Heterocycles201999164966010.3987/COM‑18‑S(F)25
     [Google Scholar]
  59. ChenY. HeY.M. ZhangS. MiaoT. FanQ.H. Rapid construction of structurally diverse quinolizidines, indolizidines, and their analogues via ruthenium-catalyzed asymmetric cascade hydrogenation/reductive amination.Angew. Chem. Int. Ed.201958123809381310.1002/anie.20181264730523655
     [Google Scholar]
  60. SeippK. GeskeL. OpatzT. Marine pyrrole alkaloids.Mar. Drugs202119951410.3390/md1909051434564176
     [Google Scholar]
  61. JiangD. ChenY. WangS. Total synthesis of marine alkaloids cystodytins A-K.J. Org. Chem.20228716110631107210.1021/acs.joc.2c0131735947782
     [Google Scholar]
  62. WangC. WangS. LiH. HouY. CaoH. HuaH. LiD. Marine-derived lead fascaplysin: Pharmacological activity, total synthesis, and structural modification.Mar. Drugs202321422610.3390/md2104022637103365
     [Google Scholar]
  63. BiardJ.F. GuyotS. RoussakisC. VerbistJ.F. VercauterenJ. WeberJ.F. BoukefK. Lepadiformine, a new marine cytotoxic alkaloid from Clavelina lepadiformis Müller.Tetrahedron Lett.199435172691269410.1016/S0040‑4039(00)77007‑9
     [Google Scholar]
  64. KibayashiC AoyagiS AbeH Total synthesis of bioactive tricyclic marine alkaloids, lepadiformine and related compounds.Bull Chem Soc Jpn200376112059207410.1246/bcsj.76.2059
     [Google Scholar]
  65. WuJ.L. ChiouW.H. Diastereocontrolled formal syntheses of (±)-Lepadiformines A, B, and C and the divergent synthesis of 2-epi-Lepadiformine C through unexpected double consecutive epimerizations.J. Org. Chem.202085149051906310.1021/acs.joc.0c0096432580551
     [Google Scholar]
  66. ShimomuraM. SatoM. AzumaH. SakataJ. TokuyamaH. Total Synthesis of (-)-lepadiformine a via radical translocation-cyclization reaction.Org. Lett.20202293313331710.1021/acs.orglett.0c0047432182082
     [Google Scholar]
  67. ZhidkovM.E. SmirnovaP.A. TryapkinO.A. KantemirovA.V. KhudyakovaY.V. MalyarenkoO.S. ErmakovaS.P. GrigorchukV.P. KauneM. von AmsbergG. DyshlovoyS.A. Total syntheses and preliminary biological evaluation of brominated fascaplysin and reticulatine alkaloids and their analogues.Mar. Drugs201917949610.3390/md1709049631450717
     [Google Scholar]
  68. WeinrebS.M. Studies on total synthesis of the cylindricine/fasicularin/lepadiformine family of tricyclic marine alkaloids.Chem. Rev.200610662531254910.1021/cr050069v16771458
     [Google Scholar]
  69. SunP. SunC. WeinrebS.M. Stereoselective total syntheses of the racemic form and the natural enantiomer of the marine alkaloid lepadiformine via a novel N-acyliminium ion/allylsilane spirocyclization strategy.J. Org. Chem.200267124337434510.1021/jo020107012054972
     [Google Scholar]
  70. SunP. SunC. WeinrebS.M. A new total synthesis of the marine tunicate alkaloid lepadiformine.Org. Lett.20013223507351010.1021/ol010179y11678694
     [Google Scholar]
  71. SunP. Total synthesis of the marine alkaloid (±)-lepadiformine via a radical carboazidation.Angew. Chem. Int. Ed.20001223398910.1021/ol060083
     [Google Scholar]
  72. SchärP. RenaudP. Total synthesis of the marine alkaloid (+/-)-lepadiformine via a radical carboazidation.Org. Lett.2006881569157110.1021/ol060083+16597112
     [Google Scholar]
  73. StorkG. BrizzolaraA. LandesmanH. SzmuszkoviczJ. TerrellR. The enamine alkylation and acylation of carbonyl compounds.J. Am. Chem. Soc.196385220722210.1021/ja00885a021
     [Google Scholar]
  74. KauffmannT. AbelnR. WelkeS. WingbermühleD. Carbonylofefinierende Carbenwolframkomplexe und ihre Eignung als Olefinmetathese‐Katalysatoren.Angew. Chem.1986981092792810.1002/ange.19860981025
     [Google Scholar]
  75. PearsonW.H. BartaN.S. KampfJ.W. Synthetic studies on the perhydropyrrolo[2,1-j]quinoline marine alkaloids lepadiformine and cylindricine C using a 2-azapentadienyl anion cycloaddition. Synthesis of 2,13-diepilepadiformine (or 2-epi-11-deoxycylindricine C).Tetrahedron Lett.199738193369337210.1016/S0040‑4039(97)00632‑1
     [Google Scholar]
  76. PanchaudP. RenaudP. 3-Pyridinesulfonyl azide: A useful reagent for radical azidation.Adv. Synth. Catal.2004346892592810.1002/adsc.200404038
     [Google Scholar]
  77. ThomsenI. ClausenK. ScheibyeS. LawessonS. Thiation with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide: N-methylthiopyrrolidone.Org. Synth.19846215816110.15227/orgsyn.062.0158
     [Google Scholar]
  78. TsukanovS.V. MarksL.R. CominsD.L. Studies toward the Synthesis of Lepadiformine A.J. Org. Chem.20168121104331044310.1021/acs.joc.6b0151427626463
     [Google Scholar]
  79. YoshimuraA. HanzawaR. FuwaH. Stereoselective tandem synthesis of pyrrolidine derivatives under gold catalysis: An asymmetric synthesis of (-)Lepadiformine A.Org. Lett.202224346237624110.1021/acs.orglett.2c0200735849685
     [Google Scholar]
  80. HanzawaR. FuwaH. Collective asymmetric total synthesis of cylindricines.Org. Lett.202325111984198810.1021/acs.orglett.3c0055136912364
     [Google Scholar]
/content/journals/cos/10.2174/0115701794332632240918043021
Loading
Advances in the Total Synthesis of Pharmacologically Important Fused Indolizidine Alkaloids: Securinine, Gephyrotoxin and Lepadiformine
Curr. Org. Synth. 22, 288 (2025); https://doi.org/10.2174/0115701794332632240918043021
/content/journals/cos/10.2174/0115701794332632240918043021
/content/journals/cos/10.2174/0115701794332632240918043021
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): gephyrotoxin; indolizidine alkaloids; lepadiformine; securinine; stereochemistry; Synthesis

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