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2000
Volume 21, Issue 4
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646

Abstract

Cancer poses a significant threat to human life and well-being, resulting in numerous individuals suffering and succumbing to various forms of the disease each year. Considerable resources have been allocated to combat cancer, yet the limitations of existing anticancer agents, including their side effects and the development of drug resistance, have left substantial challenges in our quest to conquer cancer. Thus, there is an urgent necessity to discover and develop novel chemical compounds with the potential to inhibit cancer growth. In this review, we primarily focus on examining the effectiveness of two distinct classes of carbazole-based compounds: carboline derivatives and diazacarbazole derivatives. Diazacarbazole derivatives, a relatively unexplored area, hold promise for offering a fresh perspective and valuable opportunities to overcome the formidable obstacles in the ongoing battle against cancer. Additionally, we present several synthetic methods for creating the essential structural frameworks of carbazole-based tricyclic compounds.

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2024-06-05
2025-10-11
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References

  1. WHO methods and data sources for global burden of disease estimates 2000–2015, Department of information, evidence and research WHO, Geneva, January 2017.Available from: http://www.who.int/healthinfo/global_burden_disease/GlobalDALYmethods_2000_2015.pdf
  2. FerlayJ. SoerjomataramI. DikshitR. EserS. MathersC. RebeloM. ParkinD.M. FormanD. BrayF. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012.Int. J. Cancer20151365E359E38610.1002/ijc.2921025220842
    [Google Scholar]
  3. SchmidtA.W. ReddyK.R. KnölkerH.J. Occurrence, biogenesis, and synthesis of biologically active carbazole alkaloids.Chem. Rev.201211263193332810.1021/cr200447s22480243
    [Google Scholar]
  4. KnölkerH.J. ReddyK.R. Isolation and synthesis of biologically active carbazole alkaloids.Chem. Rev.2002102114303442810.1021/cr020059j12428991
    [Google Scholar]
  5. GraebeC. GlazerC. First isolation of carbazole from coal tar.Chem. Ber.1872512
    [Google Scholar]
  6. ChakrabortyD.P. RoyS. Carbazole alkaloids IV.Fortschritte der Chemie organischer Naturstoffe/Progress in the Chemistry of Organic Natural Products.Wien GmbHSpringer-Verlag20038512523010.1007/978‑3‑7091‑6051‑0_3
    [Google Scholar]
  7. BashirM. BanoA. IjazA. ChaudharyB. Recent developments and biological activities of N-substituted carbazole derivatives: A review.Molecules2015208134961351710.3390/molecules20081349626213906
    [Google Scholar]
  8. BajajY.P.S. OchosiaS.P. In vitro production of ellipticine an antitumor agent. Ch enieuxC. RamawatKG. RideauM. Medicinal and aromatic plants I. Biotechnology in agriculture and forestryBerlin HeidelbergSpringer-Verlag198824
    [Google Scholar]
  9. SinicropiM.S. IacopettaD. RosanoC. Randino, R.; Caruso, A.; Saturnino, C.; Muià, a Jessica Ceramella, N.; Puoci, F.; Rodriquez, M.; Longo, P.; Plutino, M. R.; N-thioalkylcarbazoles derivatives as new anti-proliferative agents: synthesis, characterization, and molecular mechanism evaluation.J. Enzyme Inhib. Med. Chem.20183343444410.1080/14756366.2017.141921629383954
    [Google Scholar]
  10. JiangH. ZhangW.J. LiP.H. WangJ. DongC.Z. ZhangK. ChenH.X. DuZ.Y. Synthesis and biological evaluation of novel carbazole-rhodanine conjugates as topoisomerase II inhibitors.Bioorg. Med. Chem. Lett.20182881320132310.1016/j.bmcl.2018.03.01729545100
    [Google Scholar]
  11. SaturninoC. CarusoA. IacopettaD. Rosano, C.; Ceramella, J.; Muià, N.; Mariconda,A.; Bonomo, M-G.; Ponassi, M.; Rosace, G.; Sinicropi, M.S.; Longo,P. Inhibition of human topoisomerase II by new N,N,N-trimethylethanammonium iodide alkylcarbazole derivatives.Chem.Med.Chem.2018132635264310.1002/cmdc.20180054630347518
    [Google Scholar]
  12. Alectinib approved for (ALK) positive metastatic non-small cell lung cancer (NSCLC), U.S. FDA, Approved Drugs, available at : https://www.fda.gov/Drugs/InformationOnDrugs/ ApprovedDrugs/ucm584082.htm [last accessed 26 Apr 2018].
  13. Ruiz-CejaK.A. ChirinoY.I. Current FDA-approved treatments for non-small cell lung cancer and potential biomarkers for its detection.Biomed. Pharmacother.20179090243710.1016/j.biopha.2017.03.01828340378
    [Google Scholar]
  14. Midostaurin approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML), U.S. FDA, Approved Drugs, available at : https://www.fda.gov/ Drugs/InformationOnDrugs/ApprovedDrugs/ucm555756. htm [last accessed 26 Apr 2018].
  15. Rydapt, midostaurin, product information, EMA, Human medicines, available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004095/ human_med_002155.jsp [last accessed 26 Jul 2018].
  16. StoneR.M. ManleyP.W. LarsonR.A. CapdevilleR. Midostaurin: Its odyssey from discovery to approval for treating acute myeloid leukemia and advanced systemic mastocytosis.Blood Adv.20182444445310.1182/bloodadvances.201701108029487059
    [Google Scholar]
  17. GutierrezL. JangM. ZhangT. AkhtariM. AlachkarH. Midostaurin reduces regulatory T cells markers in acute myeloid leukemia.Sci. Rep.2018811754410.1038/s41598‑018‑35978‑030510164
    [Google Scholar]
  18. JanosikT. RannugA. RannugU. WahlströmN. SlättJ. BergmanJ. Chemistry and properties of indolocarbazoles.Chem. Rev.2018118189058912810.1021/acs.chemrev.8b0018630191712
    [Google Scholar]
  19. TsutsumiL.S. GündischD. SunD. Carbazole € scaffold in medicinal chemistry and natural products: A review from 2010-2015. Curr. Top. Med. Chem.201616111290131310.2174/156802661566615091511264726369811
    [Google Scholar]
  20. ShaikhM. KarpoormathR. ThapliyalN. RaneR. PalkarM. FayaA.M. PatelH. AlwanW. JainK. HampannavarG. Current perspective of natural alkaloid carbazole and its derivatives as antitumor agents.Anticancer. Agents Med. Chem.20151581049106510.2174/187152061566615011310540525584693
    [Google Scholar]
  21. Council of Scientific & Industrial Research (IN). Carbazolebonded pyrrolo[2,1-c][1,4]benzodiazepine hybrids as potential anticancer agents and process for their preparation.US PATENT 8927538/20152015.
  22. Squibb CoB.M. Carbazole and carboline kinase inhibitors.US Patent 00589882012.
  23. MorrisP. Products SA Carbazole and carboline derivatives, and preparation and therapeutic applications there of.US Patent 02742582011.
  24. University of KansasFormulations of indole-3-carbinol derived antitumor agents with increased oral bioavailability.US Patent 01845902012.
  25. CNRSUse of carbazole phenone derivatives for the treatment of cancer.FR Patent 00514912012.
  26. Bristol-Meyers Squibb CoCarbazole compounds useful as bromodomain inhibitors.Patent EP 29617482018.
  27. Health Research IncCompounds and methods for treating cancers.Patent US 00240832016.
  28. IncuronL.C.C. Carbazole compounds and therapeutic uses of the compounds.Patent US 91089162015.
  29. Novogen LtdFunctionalized and substituted carbazoles as anti-cancer agents.Patent US 01586362017.
  30. GTx IncSelective androgen receptor degrader (SARD) ligands and methods of use thereof.Patent US 01665262017.
  31. Philip Morris ProductsS.A. Carbazole and carboline derivatives, and preparation and therapeutic applications thereof.Patent US 02742582013.
  32. Council of Scientific & Industrial Research (IN)Carbazolebonded pyrrolo[2,1-c][1,4]benzodiazepine hybrids as potential anticancer agents and process for their preparation.Patent US 89275382015.
  33. Bristol-Meyers Squibb CoCarbazole and carboline kinase inhibitors.Patent US 00589882013.
  34. Carbazole ehop-016 derivatives as other anti cancer and anti migratory agents.US patent 10729689B22018.
  35. New carbazoles derivatives sensitizing cells to anticancer agents.WO patent 2021/069736A12019.
  36. SunL. WuY. LiuY. ChenX. HuL. Novel carbazole sulfonamide derivatives of antitumor agent: Synthesis, antiproliferative activity and aqueous solubility.Bioorg. Med. Chem. Lett.201727226126510.1016/j.bmcl.2016.11.06827919655
    [Google Scholar]
  37. NiuF. LiuY. JingZ. HanG. SunL. YanL. ZhouL. WuY. XuY. HuL. ZhaoX. Novel carbazole sulfonamide microtubule-destabilizing agents exert potent antitumor activity against esophageal squamous cell carcinoma.Cancer Lett.2018420607110.1016/j.canlet.2018.01.06629408653
    [Google Scholar]
  38. LiuY. WuY. Sun GuY. HuL. Synthesis and structure-activity relationship study of water-soluble carbazole sulfonamide derivatives as new anticancer agents.Eur. J. Med. Chem.202019111218110.1016/j.ejmech.2020.11218132113125
    [Google Scholar]
  39. GaoZ. ChenY. NieY. ChenK. CaoX. KeS. Structural diversity-guided optimization of carbazole derivatives as potential cytotoxic agents.Front Chem.202311110486810.3389/fchem.2023.110486836742033
    [Google Scholar]
  40. KalathiyaU. PadariyaM. BaginskiM. Molecular modeling and evaluation of novel dibenzopyrrole derivatives as telomerase inhibitors and potential drug for cancer therapy.IEEE/ACM Trans Comput Biol Bioinform20141161196120710.1109/TCBB.2014.2326860
    [Google Scholar]
  41. VlaarC.P. Castillo-PichardoL. MedinaJ.I. Marrero-SerraC.M. VélezE. RamosZ. HernándezE. Design, synthesis and biological evaluation of new carbazole derivatives as anti-cancer and anti-migratory agents.Bioorg. Med. Chem.201826488489010.1016/j.bmc.2018.01.00329358027
    [Google Scholar]
  42. Butler-FernándezK.M. RamosZ. Francis-MalavéA.M. BloomJ. DharmawardhaneS. HernándezE. Synthesis, anti-cancer and anti-migratory evaluation of 3,6-dibromocarbazole and 5-bromoindole derivatives.Molecules20192415268610.3390/molecules2415268631344865
    [Google Scholar]
  43. CarusoA. SinicropiM.S. LancelotJ.C. El-KashefH. SaturninoC. AubertG. BallandonneC. LesnardA. CresteilT. DallemagneP. RaultS. Synthesis and evaluation of cytotoxic activities of new guanidines derived from carbazoles.Bioorg. Med. Chem. Lett.201424246747210.1016/j.bmcl.2013.12.04724374274
    [Google Scholar]
  44. SantioN.M. VahakoskiR.L. RainioE.M. SandholmJ.A. VirtanenS.S. PrudhommeM. AnizonF. MoreauP. KoskinenP.J. Pim-selective inhibitor DHPCC-9 reveals Pim kinases as potent stimulators of cancer cell migration and invasion.Mol. Cancer20109127910.1186/1476‑4598‑9‑27920958956
    [Google Scholar]
  45. Akué-GéduR. LetribotB. SauguesE. DebitonE. AnizonF. MoreauP. Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo[2,3-a]carbazole derivatives.Bioorg. Med. Chem. Lett.201222113807380910.1016/j.bmcl.2012.03.09822543026
    [Google Scholar]
  46. LetribotB. Akué-GéduR. SantioN.M. El-GhozziM. AvignantD. CisnettiF. KoskinenP.J. GautierA. AnizonF. MoreauP. Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors.Eur. J. Med. Chem.20125030431010.1016/j.ejmech.2012.02.00922386260
    [Google Scholar]
  47. SathiyachandranP. ManogaranP. NesterovV.N. PadmaV.V. Rajendra PrasadK.J. Design and synthesis of novel pyrrolo[2,3-a]carbazoles: 7-Chloro-2-oxo-3a-(2′-oxo-2′,3′-dihydro-1′H-indol-3′-yl)-2,3,3a,4,5,10-hexahydro-pyrrolo[3,2-a]carbazole-1-carbonitrile as an efficient anticancer agent.Eur. J. Med. Chem.201815085186310.1016/j.ejmech.2018.03.05629597168
    [Google Scholar]
  48. KinoshitaK. AsohK. FuruichiN. ItoT. KawadaH. HaraS. OhwadaJ. MiyagiT. KobayashiT. TakanashiK. TsukaguchiT. SakamotoH. TsukudaT. OikawaN. Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802).Bioorg. Med. Chem.20122031271128010.1016/j.bmc.2011.12.02122225917
    [Google Scholar]
  49. RavichandiranP. JeganA. PremnathD. PeriasamyV.S. MuthusubramanianS. VasanthkumarS. Synthesis, molecular docking and cytotoxicity evaluation of novel 2-(4-amino-benzosulfonyl)-5H-benzo[b]carbazole-6,11-dione derivatives as histone deacetylase (HDAC8) inhibitors.Bioorg. Chem.201453243610.1016/j.bioorg.2014.01.00224561820
    [Google Scholar]
  50. SisodiyaS. PaulS. ChaudharyH. GrewalP. KumarG. DanielD.P. DasB. NayakD. GuchhaitS.K. KunduC.N. BanerjeeU.C. Exploration of Benzo[b]carbazole-6,11-diones as anticancer agents: Synthesis and studies of hTopoIIα inhibition and apoptotic effects.Bioorg. Med. Chem. Lett.20214912827410.1016/j.bmcl.2021.12827434303812
    [Google Scholar]
  51. PadmajaP. Koteswara RaoG. IndrasenaA. Subba ReddyB.V. PatelN. ShaikA.B. ReddyN. DubeyP.K. BhadraM.P. Synthesis and biological evaluation of novel pyrano[3,2-c]carbazole derivatives as anti-tumor agents inducing apoptosis via tubulin polymerization inhibition.Org. Biomol. Chem.20151351404141410.1039/C4OB02015D25467166
    [Google Scholar]
  52. UvaraniC. JaivelN. SankaranM. ChandraprakashK. AtaA. MohanP.S. Axially chiral biscarbazoles and biological evaluation of the constituents from Murraya koenigii.Fitoterapia201494102010.1016/j.fitote.2014.01.00424444889
    [Google Scholar]
  53. EsvanY.J. GiraudF. PereiraE. SuchaudV. NautonL. ThéryV. DezhenkovaL.G. KaluzhnyD.N. MazovV.N. ShtilA.A. AnizonF. MoreauP. Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c.Bioorg. Med. Chem.201624143116312410.1016/j.bmc.2016.05.03227255178
    [Google Scholar]
  54. IssaS. WalchshoferN. KassabI. TermossH. ChamatS. GeahchanA. BouazizZ. Synthesis and antiproliferative activity of oxazinocarbazole and N,N-bis(carbazolylmethyl)amine derivatives.Eur. J. Med. Chem.20104562567257710.1016/j.ejmech.2010.02.04520236739
    [Google Scholar]
  55. IssaS. PrandinaA. BedelN. RongvedP. YousS. Le BorgneM. BouazizZ. Carbazole scaffolds in cancer therapy: A review from 2012 to 2018.J. Enzyme Inhib. Med. Chem.20193411321134610.1080/14756366.2019.164069231328585
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): Cancer; carbazole; coal tar; drug; fungi; scaffolds
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