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  3. Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents)
  4. Volume 22, Issue 2
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Volume 22, Issue 2
  • ISSN: 1871-5257
  • E-ISSN: 1875-6182

Abstract

Background

Glioblastoma multiforme (GBM) is characterized by massive tumor-induced angiogenesis aiding tumorigenesis. Vascular endothelial growth factor A (VEGF-A) VEGF receptor 2 (VEGFR-2) constitutes majorly to drive this process. Putting a halt to tumor-driven angiogenesis is a major clinical challenge, and the blood-brain barrier (BBB) is the prime bottleneck in GBM treatment. Several phytochemicals show promising antiangiogenic activity across different models, but their ability to cross BBB remains unexplored.

Methods

We screened over 99 phytochemicals having anti-angiogenic properties reported in the literature and evaluated them for their BBB permeability, molecular interaction with VEGFR-2 domains, ECD2-3 (extracellular domains 2-3) and TKD (tyrosine kinase domain) at VEGF-A and ATP binding site, cell membrane permeability, and hepatotoxicity using tools. Furthermore, the anti-angiogenic activity of predicted lead Trans-Chalcone (TC) was evaluated in the chick chorioallantoic membrane.

Results

Out of 99 phytochemicals, 35 showed an efficient ability to cross BBB with a probability score of > 0.8. Docking studies revealed 30 phytochemicals crossing benchmark binding affinity < -6.4 kcal/mol of TKD with the native ligand ATP alone. Out of 30 phytochemicals, 12 showed moderate to low hepatotoxicity, and 5 showed a violation of Lipinski’s rule of five. Our analysis predicted TC as a BBB permeable anti-angiogenic compound for use in GBM therapy. TC reduced vascularization in the CAM model, which was associated with the downregulation of VEGFR-2 transcript expression.

Conclusion

The present study showed TC to possess anti-angiogenic potential the inhibition of VEGFR-2. In addition, the study predicted TC to cross BBB as well as a safe alternative for GBM therapy, which needs further investigation.

© 2024 Bentham Science Publishers
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2024-11-26

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References

  1. TamimiA.F. JuweidM. Epidemiology and outcome of glioblastoma.GlioblastomaCodon PublicationsBrisbane (AU)201710.15586/codon.glioblastoma.2017.ch8
     [Google Scholar]
  2. NørøxeD.S. PoulsenH.S. LassenU. Hallmarks of glioblastoma: A systematic review.ESMO Open201616e00014410.1136/esmoopen‑2016‑00014428912963
     [Google Scholar]
  3. AhirB.K. EngelhardH.H. LakkaS.S. Tumor development and angiogenesis in adult brain tumor.Glioblastoma. Mol. Neurobiol.20205752461247810.1007/s12035‑020‑01892‑832152825
     [Google Scholar]
  4. XuC. WuX. ZhuJ. VEGF promotes proliferation of human glioblastoma multiforme stem-like cells through VEGF receptor 2.ScientificWorldJournal201320131810.1155/2013/41741323533349
     [Google Scholar]
  5. KimY.H. LeeW.W. ParkC.G. implications of calcineurin/nfat inhibitors’ regulation of dendritic cells and innate immune cells in islet xenotransplantation.J. Bacteriol. Virol.2016461110.4167/jbv.2016.46.1.1
     [Google Scholar]
  6. WangX. BoveA.M. SimoneG. MaB. Molecular bases of VEGFR-2-mediated physiological function and pathological role.Front. Cell Dev. Biol.2020859928110.3389/fcell.2020.59928133304904
     [Google Scholar]
  7. EvansI.M. BrittonG. ZacharyI.C. Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase.Cell. Signal.20082071375138410.1016/j.cellsig.2008.03.00218440775
     [Google Scholar]
  8. HolmqvistK. CrossM.J. RolnyC. HägerkvistR. RahimiN. MatsumotoT. Claesson-WelshL. WelshM. The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration.J. Biol. Chem.200427921222672227510.1074/jbc.M31272920015026417
     [Google Scholar]
  9. LamaliceL. HouleF. JourdanG. HuotJ. Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38.Oncogene200423243444510.1038/sj.onc.120703414724572
     [Google Scholar]
  10. Abu-GhazalehR. KabirJ. JiaH. LoboM. ZacharyI. Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells.Biochem. J.2001360125526410.1042/bj360025511696015
     [Google Scholar]
  11. NapioneL. AlvaroM. BussolinoF. VEGF-mediated signal transduction in tumor angiogenesis.Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy.InTech201710.5772/66764
     [Google Scholar]
  12. NavisA.C. BourgonjeA. WesselingP. WrightA. HendriksW. VerrijpK. van der LaakJ.A.W.M. HeerschapA. LeendersW.P.J. Effects of dual targeting of tumor cells and stroma in human glioblastoma xenografts with a tyrosine kinase inhibitor against c-MET and VEGFR2.PLoS One201383e5826210.1371/journal.pone.005826223484006
     [Google Scholar]
  13. LiY. AliS. ClarkeJ. ChaS. Bevacizumab in recurrent glioma: Patterns of treatment failure and implications.Brain Tumor Res. Treat.2017511910.14791/btrt.2017.5.1.128516072
     [Google Scholar]
  14. MichaelsenS.R. StabergM. PedersenH. JensenK.E. MajewskiW. BroholmH. NedergaardM.K. MeulengrachtC. UrupT. VillingshøjM. LukacovaS. Skjøth-RasmussenJ. BrennumJ. KjærA. LassenU. StockhausenM.T. PoulsenH.S. HamerlikP. VEGF-C sustains VEGFR2 activation under bevacizumab therapy and promotes glioblastoma maintenance.Neuro Oncol.201820111462147410.1093/neuonc/noy10329939339
     [Google Scholar]
  15. ThomsonR.J. MoshirfarM. RonquilloY. Tyrosine Kinase Inhibitors.Treasure Island, FLStatPearls2021
     [Google Scholar]
  16. FatimaN. BaqriS.S.R. AlsulimaniA. FagooneeS. SlamaP. KesariK.K. RoychoudhuryS. HaqueS. Phytochemicals from indian ethnomedicines: Promising prospects for the management of oxidative stress and cancer.Antioxidants20211010160610.3390/antiox1010160634679741
     [Google Scholar]
  17. ChoudhariA.S. MandaveP.C. DeshpandeM. RanjekarP. PrakashO. Phytochemicals in cancer treatment: From preclinical studies to clinical practice.Front. Pharmacol.202010161410.3389/fphar.2019.0161432116665
     [Google Scholar]
  18. Van TellingenO. Yetkin-ArikB. de GooijerM.C. WesselingP. WurdingerT. de VriesH.E. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment.Drug Resist. Updat.20151911210.1016/j.drup.2015.02.00225791797
     [Google Scholar]
  19. BellettatoC.M. ScarpaM. Possible strategies to cross the blood-brain barrier.Ital. J. Pediatr.201844S213110.1186/s13052‑018‑0563‑030442184
     [Google Scholar]
  20. ShakerB. AhmadS. LeeJ. JungC. NaD. In silico methods and tools for drug discovery.Comput. Biol. Med.202113710485110.1016/j.compbiomed.2021.10485134520990
     [Google Scholar]
  21. PubMedAvailable from: https://pubmed.ncbi.nlm.nih.gov/
  22. GoogleAvailable from: https://www.google.com/
  23. ChengF. LiW. ZhouY. ShenJ. WuZ. LiuG. LeeP.W. TangY. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties.J. Chem. Inf. Model.201252113099310510.1021/ci300367a23092397
     [Google Scholar]
  24. XiongG. WuZ. YiJ. FuL. YangZ. HsiehC. YinM. ZengX. WuC. LuA. ChenX. HouT. CaoD. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties.Nucleic Acids Res.202149W1W5W1410.1093/nar/gkab25533893803
     [Google Scholar]
  25. PiresD.E.V. BlundellT.L. AscherD.B. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures.J. Med. Chem.20155894066407210.1021/acs.jmedchem.5b0010425860834
     [Google Scholar]
  26. DainaA. MichielinO. ZoeteV. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.Sci. Rep.2017714271710.1038/srep4271728256516
     [Google Scholar]
  27. PubChemhttps://pubchem.ncbi.nlm.nih.gov/
  28. BermanH.M. WestbrookJ. FengZ. GillilandG. BhatT.N. WeissigH. ShindyalovI.N. BourneP.E. The protein data bank.Nucleic Acids Res.200028123524210.1093/nar/28.1.23510592235
     [Google Scholar]
  29. WaterhouseA. BertoniM. BienertS. StuderG. TaurielloG. GumiennyR. HeerF.T. de BeerT.A.P. RempferC. BordoliL. LeporeR. SchwedeT. SWISS-MODEL: Homology modelling of protein structures and complexes.Nucleic Acids Res.201846W1W296W30310.1093/nar/gky42729788355
     [Google Scholar]
  30. ProteinAvailable from: https://www.ncbi.nlm.nih.gov/protein/
  31. KoJ. GalaxyWEB server for protein structure prediction and refinement.Nucleic Acids Res.201240(Web Server issue)W294710.1093/nar/gks493
     [Google Scholar]
  32. BrozzoM.S. BjelićS. KiskoK. SchleierT. LeppänenV.M. AlitaloK. WinklerF.K. Ballmer-HoferK. Thermodynamic and structural description of allosterically regulated VEGFR-2 dimerization.Blood201211971781178810.1182/blood‑2011‑11‑39092222207738
     [Google Scholar]
  33. O’BoyleN.M. BanckM. JamesC.A. MorleyC. VandermeerschT. HutchisonG.R. Open Babel: An open chemical toolbox.J. Cheminform.2011313310.1186/1758‑2946‑3‑3321982300
     [Google Scholar]
  34. LipinskiC.A. LombardoF. DominyB.W. FeeneyP.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.Adv. Drug Deliv. Rev.2001461-332610.1016/S0169‑409X(00)00129‑011259830
     [Google Scholar]
  35. RibattiD. NicoB. VaccaA. PrestaM. The gelatin sponge-chorioallantoic membrane assay.Nat. Protoc.200611859110.1038/nprot.2006.1317406216
     [Google Scholar]
  36. CloneyK. Franz-OdendaalT.A. Optimized ex-ovo culturing of chick embryos to advanced stages of development.J. Vis. Exp.2015955212925650550
     [Google Scholar]
  37. KueC.S. TanK.Y. LamM.L. LeeH.B. Chick embryo chorioallantoic membrane (CAM): An alternative predictive model in acute toxicological studies for anti-cancer drugs.Exp. Anim.201564212913810.1538/expanim.14‑005925736707
     [Google Scholar]
  38. HubrechtR.C. CarterE. The 3Rs and humane experimental technique: Implementing change.Animals201991075410.3390/ani910075431575048
     [Google Scholar]
  39. BhatA. SharmaA. BhartiA.C. Upstream hedgehog signaling components are exported in exosomes of cervical cancer cell lines.Nanomedicine201813172127213810.2217/nnm‑2018‑014330265222
     [Google Scholar]
  40. VishnoiK. MahataS. TyagiA. PandeyA. VermaG. JadliM. SinghT. SinghS.M. BhartiA.C. Cross-talk between human papillomavirus oncoproteins and hedgehog signaling synergistically promotes stemness in cervical cancer cells.Sci. Rep.2016613437710.1038/srep3437727678330
     [Google Scholar]
  41. JakaO. IturriaI. van der ToornM. Hurtado de MendozaJ. LatinoD.A.R.S. AlzualdeA. PeitschM.C. HoengJ. KoshibuK. Effects of natural monoamine oxidase inhibitors on anxiety-like behavior in zebrafish.Front. Pharmacol.20211266937010.3389/fphar.2021.66937034079463
     [Google Scholar]
  42. Djinovic-CarugoK. CarugoO. Missing strings of residues in protein crystal structures.Intrinsically Disord. Proteins201531e109569710.1080/21690707.2015.109569728232893
     [Google Scholar]
  43. FongG.H. RossantJ. GertsensteinM. BreitmanM.L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium.Nature19953766535667010.1038/376066a07596436
     [Google Scholar]
  44. HiratsukaS. MinowaO. KunoJ. NodaT. ShibuyaM. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice.Proc. Natl. Acad. Sci.199895169349935410.1073/pnas.95.16.93499689083
     [Google Scholar]
  45. MullerY.A. LiB. ChristingerH.W. WellsJ.A. CunninghamB.C. de VosA.M. Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site.Proc. Natl. Acad. Sci.199794147192719710.1073/pnas.94.14.71929207067
     [Google Scholar]
  46. RoskoskiR. Jr Vascular endothelial growth factor (VEGF) and VEGF receptor inhibitors in the treatment of renal cell carcinomas.Pharmacol. Res.201712011613210.1016/j.phrs.2017.03.01028330784
     [Google Scholar]
  47. LeppänenV.M. ProtaA.E. JeltschM. AnisimovA. KalkkinenN. StrandinT. LankinenH. GoldmanA. Ballmer-HoferK. AlitaloK. Structural determinants of growth factor binding and specificity by VEGF receptor 2.Proc. Natl. Acad. Sci.201010762425243010.1073/pnas.091431810720145116
     [Google Scholar]
  48. ShaikF. CuthbertG. Homer-VanniasinkamS. MuenchS. PonnambalamS. HarrisonM. Structural basis for vascular endothelial growth factor receptor activation and implications for disease therapy.Biomolecules20201012167310.3390/biom1012167333333800
     [Google Scholar]
  49. WangL. ChenN. ChengH. Fisetin inhibits vascular endothelial growth factor-induced angiogenesis in retinoblastoma cells.Oncol. Lett.20202021239124410.3892/ol.2020.1167932724364
     [Google Scholar]
  50. ModiS.J. KulkarniV.M. Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: Medicinal chemistry perspective.Med. Drug Discov.20192100009
     [Google Scholar]
  51. GonzálezI. ChatterjeeD. Histopathological features of drug-induced liver injury secondary to osimertinib.ACG Case Rep. J.201962e0001110.14309/crj.000000000000001131616716
     [Google Scholar]
  52. GuanL.P. NanJ.X. JinX.J. JinQ.H. KwakK.C. ChaiK. QuanZ.S. Protective effects of chalcone derivatives for acute liver injury in mice.Arch. Pharm. Res.2005281818610.1007/BF0297514015742813
     [Google Scholar]
  53. ShenJ. ChengF. XuY. LiW. TangY. Estimation of ADME properties with substructure pattern recognition.J. Chem. Inf. Model.20105061034104110.1021/ci100104j20578727
     [Google Scholar]
  54. AzadI. NasibullahM. KhanT. HassanF. AkhterY. Exploring the novel heterocyclic derivatives as lead molecules for design and development of potent anticancer agents.J. Mol. Graph. Model.20188121122810.1016/j.jmgm.2018.02.01329609141
     [Google Scholar]
  55. OyedaraO.O. AgbedahunsiJ.M. AdeyemiF.M. Juárez-SaldivarA. FadareO.A. AdetunjiC.O. RiveraG. Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection. Phytomed.Plus20211410013510.1016/j.phyplu.2021.10013535403085
     [Google Scholar]
  56. ZhangL. WuY. YangG. GanH. SangD. ZhouJ. SuL. WangR. MaL. Design, synthesis and biological evaluation of novel osthole-based derivatives as potential neuroprotective agents.Bioorg. Med. Chem. Lett.2020302412763310.1016/j.bmcl.2020.12763333132198
     [Google Scholar]
  57. SchwedeT. KoppJ. GuexN. PeitschM.C. SWISS-MODEL: An automated protein homology-modeling server.Nucleic Acids Res.200331133381338510.1093/nar/gkg52012824332
     [Google Scholar]
  58. LaskowskiR.A. PROCHECK: A program to check the stereochemical quality of protein structures.J. Appl. Crystall.1993262283291
     [Google Scholar]
  59. EisenbergD. LüthyR. BowieJ.U. VERIFY3D: Assessment of protein models with three-dimensional profiles.Methods Enzymol.199727739640410.1016/S0076‑6879(97)77022‑89379925
     [Google Scholar]
  60. DhanavadeM.J. JalkuteC.B. BarageS.H. SonawaneK.D. Homology modeling, molecular docking and MD simulation studies to investigate role of cysteine protease from Xanthomonas campestris in degradation of Aβ peptide.Comput. Biol. Med.201343122063207010.1016/j.compbiomed.2013.09.02124290922
     [Google Scholar]
  61. KooteryK.P. SarojiniS. Structural and functional characterization of a hypothetical protein in the RD7 region in clinical isolates of Mycobacterium tuberculosis - an in silico approach to candidate vaccines.J. Genet. Eng. Biotechnol.20222015510.1186/s43141‑022‑00340‑535394551
     [Google Scholar]
  62. LakhliliW. ChevéG. YasriA. IbrahimiA. Determination and validation of mTOR kinase-domain 3D structure by homology modeling.OncoTargets Ther.201581923193010.2147/OTT.S8420026257525
     [Google Scholar]
  63. TrottO. OlsonA.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem.201031245546119499576
     [Google Scholar]
  64. ChenZ. LinT. LiaoX. LiZ. LinR. QiX. ChenG. SunL. LinL. Network pharmacology based research into the effect and mechanism of yinchenhao decoction against cholangiocarcinoma.Chin. Med.20211611310.1186/s13020‑021‑00423‑433478536
     [Google Scholar]
  65. QawooghaS.S. ShahiwalaA. Identification of potential anticancer phytochemicals against colorectal cancer by structure-based docking studies.J. Recept. Signal Transduct. Res.2020401677610.1080/10799893.2020.171543131971455
     [Google Scholar]
  66. JinF. XieT. HuangX. ZhaoX. Berberine inhibits angiogenesis in glioblastoma xenografts by targeting the VEGFR2/ERK pathway.Pharm. Biol.201856166567110.1080/13880209.2018.154862731070539
     [Google Scholar]
  67. MaW. ZhuM. ZhangD. YangL. YangT. LiX. ZhangY. Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2.Phytomedicine201725455110.1016/j.phymed.2016.12.01328190470
     [Google Scholar]
  68. KangsamaksinT. ChaithongyotS. WootthichairangsanC. HanchainaR. TangshewinsirikulC. SvastiJ. Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α.PLoS One20171212e018962810.1371/journal.pone.018962829232409
     [Google Scholar]
  69. XuX. WuL. ZhouX. ZhouN. ZhuangQ. YangJ. DaiJ. WangH. ChenS. MaoW. Cryptotanshinone inhibits VEGF-induced angiogenesis by targeting the VEGFR2 signaling pathway.Microvasc. Res.2017111253110.1016/j.mvr.2016.12.01128040437
     [Google Scholar]
  70. NofiantiK.A. EkowatiJ. o -Hydroxycinnamic derivatives as prospective anti-platelet candidates: In silico pharmacokinetic screening and evaluation of their binding sites on COX-1 and P2Y 12 receptors.J. Basic Clin. Physiol. Pharmacol.20193062019032710.1515/jbcpp‑2019‑032731855569
     [Google Scholar]
  71. MuhammadA. KatsayalB.S. ForcadosG.E. MalamiI. AbubakarI.B. kandiA.I. IdrisA.M. YusufS. MusaS.M. MondayN. UmarZ.S. In silico predictions on the possible mechanism of action of selected bioactive compounds against breast cancer.in silico Pharmacol.202081410.1007/s40203‑020‑00057‑833194532
     [Google Scholar]
  72. IbrahimZ.Y. UzairuA. ShallangwaG.A. AbechiS.E. Application of QSAR method in the design of enhanced antimalarial derivatives of azetidine-2-carbonitriles, their molecular docking, drug-likeness, and swissadme properties.Iran. J. Pharm. Res.202120325427034903987
     [Google Scholar]
  73. OhK.K. AdnanM. ChoD.H. Network pharmacology-based study to uncover potential pharmacological mechanisms of korean thistle (cirsium japonicum var. maackii (maxim.) matsum.) flower against cancer.Molecules20212619590410.3390/molecules2619590434641448
     [Google Scholar]
  74. LiM. The in ovo chick Chorioallantoic Membrane (CAM) assay as an efficient xenograft model of hepatocellular carcinoma.J. Vis. Exp.201510452411
     [Google Scholar]
  75. KennedyD.C. CoenB. WheatleyA.M. McCullaghK.J.A. Microvascular experimentation in the chick chorioallantoic membrane as a model for screening angiogenic agents including from gene-modified cells.Int. J. Mol. Sci.202123145210.3390/ijms2301045235008876
     [Google Scholar]
  76. MeehanG.R. ScalesH.E. OsiiR. De NizM. LawtonJ.C. MartiM. GarsideP. CraigA. BrewerJ.M. Developing a xenograft model of human vasculature in the mouse ear pinna.Sci. Rep.2020101205810.1038/s41598‑020‑58650‑y32029768
     [Google Scholar]
  77. SchmidtK.M. GeisslerE.K. LangS.A. Subcutaneous murine xenograft models: A critical tool for studying human tumor growth and angiogenesis in vivo.Methods Mol. Biol.2016146412913710.1007/978‑1‑4939‑3999‑2_1227858362
     [Google Scholar]
  78. LamokeF. LabaziM. MontemariA. ParisiG. VaranoM. BartoliM. Trans-Chalcone prevents VEGF expression and retinal neovascularization in the ischemic retina.Exp. Eye Res.201193435035410.1016/j.exer.2011.02.00721354136
     [Google Scholar]
  79. RibattiD. The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model.Mech. Dev.2016141707710.1016/j.mod.2016.05.00327178379
     [Google Scholar]
  80. MaQ. ChenW. ChenW. Anti-tumor angiogenesis effect of a new compound: B-9-3 through interference with VEGFR2 signaling.Tumour Biol.20163756107611610.1007/s13277‑015‑4473‑026611645
     [Google Scholar]
  81. ShanmuganathanS. AngayarkanniN. Chebulagic acid chebulinic acid and gallic acid, the active principles of triphala, inhibit TNFα induced pro-angiogenic and pro-inflammatory activities in retinal capillary endothelial cells by inhibiting p38, ERK and NFkB phosphorylation.Vascul. Pharmacol.2018108233510.1016/j.vph.2018.04.00529678603
     [Google Scholar]
  82. TufanA. Satiroglu-TufanN. The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents.Curr. Cancer Drug Targets20055424926610.2174/156800905406462415975046
     [Google Scholar]
  83. PetrováK. BačkorováM. DemčišákováZ. PetrovováE. GogaM. VilkováM. FrenákR. BačkorM. MojžišJ. KelloM. Usnic acid isolated from Usnea antarctica (Du Rietz) reduced in vitro angiogenesis in VEGF- and bFGF-stimulated HUVECs and Ex Ovo in Quail Chorioallantoic Membrane (CAM) assay.Life2022129144410.3390/life1209144436143480
     [Google Scholar]
  84. JungM.H. LeeS.H. AhnE.M. LeeY.M. Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway.Carcinogenesis200930465566110.1093/carcin/bgp03919228635
     [Google Scholar]
  85. YuanX. YangQ. LiuT. LiK. LiuY. ZhuC. ZhangZ. LiL. ZhangC. XieM. LinJ. ZhangJ. JinY. Design, synthesis and in vitro evaluation of 6-amide-2-aryl benzoxazole/benzimidazole derivatives against tumor cells by inhibiting VEGFR-2 kinase.Eur. J. Med. Chem.201917914716510.1016/j.ejmech.2019.06.05431252306
     [Google Scholar]
  86. AlipourM.R. JeddiS. Karimi-SalesE. Trans ‐Chalcone inhibits high‐fat diet‐induced disturbances in FXR/SREBP‐1c/FAS and FXR/Smad‐3 pathways in the kidney of rats.J. Food Biochem.20204411e1347610.1111/jfbc.1347632944984
     [Google Scholar]
  87. BortolottoL.F.B. BarbosaF.R. SilvaG. BitencourtT.A. BeleboniR.O. BaekS.J. MarinsM. FachinA.L. Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest.Biomed. Pharmacother.20178542543310.1016/j.biopha.2016.11.04727903423
     [Google Scholar]
  88. KomotoT.T. LeeJ. LertpatipanpongP. RyuJ. MarinsM. FachinA.L. BaekS.J. Trans-chalcone suppresses tumor growth mediated at least in part by the induction of heme oxygenase-1 in breast cancer.Toxicol. Res.202137448549310.1007/s43188‑021‑00089‑y34631505
     [Google Scholar]
  89. Staurengo-FerrariL. Ruiz-MiyazawaK.W. Pinho-RibeiroF.A. FattoriV. ZaninelliT.H. Badaro-GarciaS. BorghiS.M. CarvalhoT.T. Alves-FilhoJ.C. CunhaT.M. CunhaF.Q. CasagrandeR. VerriW.A.Jr Trans-chalcone attenuates pain and inflammation in experimental acute gout arthritis in mice.Front. Pharmacol.20189112310.3389/fphar.2018.0112330333752
     [Google Scholar]
  90. SinghH. SidhuS. ChopraK. KhanM.U. Hepatoprotective effect of trans -Chalcone on experimentally induced hepatic injury in rats: Inhibition of hepatic inflammation and fibrosis.Can. J. Physiol. Pharmacol.201694887988710.1139/cjpp‑2016‑007127191034
     [Google Scholar]
  91. Karimi-SalesE. JeddiS. Ebrahimi-KalanA. AlipourM.R. Trans-chalcone enhances insulin sensitivity through the miR-34a/SIRT1 pathway.Iran. J. Basic Med. Sci.201821435936329796217
     [Google Scholar]
  92. MartinezR.M. Pinho-RibeiroF.A. SteffenV.S. CaviglioneC.V. FattoriV. BussmannA.J.C. BotturaC. FonsecaM.J.V. VignoliJ.A. BaracatM.M. GeorgettiS.R. VerriW.A.Jr CasagrandeR. trans-Chalcone, a flavonoid precursor, inhibits UV-induced skin inflammation and oxidative stress in mice by targeting NADPH oxidase and cytokine production.Photochem. Photobiol. Sci.20171671162117310.1039/c6pp00442c28594010
     [Google Scholar]
  93. NishidaN. YanoH. NishidaT. KamuraT. KojiroM. Angiogenesis in cancer.Vasc. Health Risk Manag.20062321321910.2147/vhrm.2006.2.3.21317326328
     [Google Scholar]
  94. ZiyadS. Iruela-ArispeM.L. Molecular mechanisms of tumor angiogenesis.Genes Cancer20112121085109610.1177/194760191143233422866200
     [Google Scholar]
  95. LeeY.S. LimS.S. ShinK.H. KimY.S. OhuchiK. JungS.H. Anti-angiogenic and anti-tumor activities of 2′-hydroxy-4′-methoxychalcone.Biol. Pharm. Bull.20062951028103110.1248/bpb.29.102816651739
     [Google Scholar]
  96. SunM. WangY. YuanM. ZhaoQ. ZhangY. YaoY. DuanY. Angiogenesis, anti-tumor, and anti-metastatic activity of novel α-substituted hetero-aromatic chalcone hybrids as inhibitors of microtubule polymerization.Front Chem.2021976620110.3389/fchem.2021.76620134900935
     [Google Scholar]
  97. YuY. W. R.G. SatoJ.D. (1998). Coding region for human VEGF receptor KDR (VEGFR-2).
     [Google Scholar]
/content/journals/chamc/10.2174/0118715257250417231019102501
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Anti-angiogenic Potential of Trans-chalcone in an In Vivo Chick Chorioallantoic Membrane Model: An ATP Antagonist to VEGFR with Predicted Blood-brain Barrier Permeability
Cardiovasc. Hematol. Agents Med. Chem. 22, 187 (2024); https://doi.org/10.2174/0118715257250417231019102501
/content/journals/chamc/10.2174/0118715257250417231019102501
/content/journals/chamc/10.2174/0118715257250417231019102501
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  • Article Type:     Research Article
Keyword(s): anti-angiogenesis; blood-brain barrier; brain parenchyma; Glioblastoma multiforme; tumor-induced-angiogenesis; VEGF

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