Skip to content
2000
Volume 30, Issue 4
  • ISSN: 1385-2728
  • E-ISSN: 1875-5348

Abstract

Indole derivatives are a significant class of organic compounds with diverse biological activities. They are found in numerous natural products and synthetic drugs, playing a crucial role in medicinal chemistry. In this comprehensive review, we have summarized the synthetic approaches and biological evaluations of a variety of indole derivatives. We analyzed and studies assessing the bioactivity of indole derivatives, focusing on structure-activity relationships. The versatility and efficacy of indole-based compounds hold great potential for advancing medical therapies, particularly in the fields of cancer treatment, infectious diseases, and inflammatory disorders. This concise review aims to inspire further research on indole-based compounds for drug development.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/coc/10.2174/0113852728382848250610051815
2025-07-02
2026-01-31

  • From This Site

    /content/journals/coc/10.2174/0113852728382848250610051815
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SharmaV. KumarP. PathakD. Biological importance of the indole nucleus in recent years: A comprehensive review.J. Heterocycl. Chem.201047349150210.1002/jhet.349
     [Google Scholar]
  2. FernándezS. ArnáizV. RufoD. ArroyoY. Current status of indole-derived marine natural products: Synthetic approaches and therapeutic applications.Mar. Drugs202422312610.3390/md22030126 38535467
     [Google Scholar]
  3. RanaM. RanjanR. Sekhar GhoshN. KumarD. SinghR. A review on indole as a cardinal scaffold for anticancer drugs development.Curr. Cancer Ther. Rev.202420437238510.2174/0115733947249518231001001728
     [Google Scholar]
  4. BariwalJ. VoskressenskyL.G. Van der EyckenE.V. Recent advances in spirocyclization of indole derivatives.Chem. Soc. Rev.201847113831384810.1039/C7CS00508C 29632917
     [Google Scholar]
  5. UmerS.M. SolangiM. KhanK.M. SaleemR.S.Z. Indole-containing natural products 2019-2022: Isolations, reappraisals, syntheses, and biological activities.Molecules202227217586 36364413
     [Google Scholar]
  6. OmarF. TareqA.M. AlqahtaniA.M. DhamaK. SayeedM.A. EmranT.B. Simal-GandaraJ. Plant-based indole alkaloids: A comprehensive overview from a pharmacological perspective.Molecules2021268229710.3390/molecules26082297 33921093
     [Google Scholar]
  7. SunP. HuangY. YangX. LiaoA. WuJ. The role of indole derivative in the growth of plants: A review.Front Plant. Sci.202313112061310.3389/fpls.2022.1120613 36726683
     [Google Scholar]
  8. BaeyerA. EmmerlingA. Synthese des Indols.Ber. Dtsch. Chem. Ges.18692167968210.1002/cber.186900201268
     [Google Scholar]
  9. HeraviM.M. AmiriZ. KafshdarzadehK. ZadsirjanV. Synthesis of indole derivatives as prevalent moieties present in selected alkaloids.RSC Advances20211153335403361210.1039/D1RA05972F 35497516
     [Google Scholar]
  10. SunH. SunK. SunJ. Recent advances of marine natural indole products in chemical and biological aspects.Molecules2023285220410.3390/molecules28052204 36903451
     [Google Scholar]
  11. TsurudaS. SatoT. AoyamaH. SirimangkalakittiN. FujimuraS. ArisawaM. MuraiK. Total synthesis and antibacterial activity of marine tris-indole alkaloid tulongicin A.J. Nat. Prod.202487615561562 38758599
     [Google Scholar]
  12. Mohammad-ZadehL.F. MosesL. Gwaltney-BrantS.M. Serotonin: A review.J. Vet. Pharmacol. Ther.200831318719910.1111/j.1365‑2885.2008.00944.x 18471139
     [Google Scholar]
  13. MoncrieffJ. CooperR.E. StockmannT. AmendolaS. HengartnerM.P. HorowitzM.A. The serotonin theory of depression: A systematic umbrella review of the evidence.Mol. Psychiatry20232883243325610.1038/s41380‑022‑01661‑0 35854107
     [Google Scholar]
  14. SimonS. PetrášekJ. Why plants need more than one type of auxin.Plant Sci.20111803454460 21421392
     [Google Scholar]
  15. ZhangB.X. LiP.S. WangY.Y. WangJ.J. LiuX.L. WangX.Y. HuX.M. Characterization and synthesis of indole-3-acetic acid in plant growth promoting Enterobacter sp.RSC Advances20211150316013160710.1039/D1RA05659J 35496854
     [Google Scholar]
  16. BunsangiamS. ThongpaeN. LimtongS. SrisukN. Large scale production of indole-3-acetic acid and evaluation of the inhibitory effect of indole-3-acetic acid on weed growth.Sci. Rep.202111113094 34158557
     [Google Scholar]
  17. KikuchiA.M. TanabeA. IwahoriY. A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning.J. Diet. Suppl.2021183316333 32272859
     [Google Scholar]
  18. SutantoC.N. LohW.W. KimJ.E. The impact of tryptophan supplementation on sleep quality: A systematic review, meta-analysis, and meta-regression.Nutr. Rev.2022802306316 33942088
     [Google Scholar]
  19. OlawaleF. AdetunjiT.L. AdetunjiA.E. IwaloyeO. FolorunsoI.M. The therapeutic value of alstonine: An updated review.S. Afr. J. Bot.202315228829510.1016/j.sajb.2022.11.047
     [Google Scholar]
  20. ElisabetskyE. Costa-CamposL. The alkaloid alstonine: A review of its pharmacological properties.Evid. Based Complement. Alternat. Med.200631394810.1093/ecam/nek011 16550222
     [Google Scholar]
  21. Tfelt-HansenP. SaxenaP.R. DahlöfC. PascualJ. LáinezM. HenryP. DienerH. SchoenenJ. FerrariM.D. GoadsbyP.J. Ergotamine in the acute treatment of migraine: A review and European consensus.Brain2000123191810.1093/brain/123.1.9 10611116
     [Google Scholar]
  22. BigalM.E. TepperS.J. Ergotamine and dihydroergotamine: A review.Curr. Pain Headache Rep.200371556210.1007/s11916‑003‑0011‑7 12525272
     [Google Scholar]
  23. KamfarW.W. KhraiweshH.M. IbrahimM.O. QadhiA.H. AzharW.F. GhafouriK.J. AlhussainM.H. AldairiA.F. AlShahraniA.M. AlghannamA.F. AbdulalR.H. Al-SlaihatA.H. QutobM.S. ElrggalM.E. GhaithM.M. AzzehF.S. Comprehensive review of melatonin as a promising nutritional and nutraceutical supplement.Heliyon2024102e2426610.1016/j.heliyon.2024.e24266 38293391
     [Google Scholar]
  24. XieZ. ChenF. LiW.A. GengX. LiC. MengX. FengY. LiuW. YuF. A review of sleep disorders and melatonin.Neurol. Res.201739655956510.1080/01616412.2017.1315864 28460563
     [Google Scholar]
  25. EmetM. OzcanH. OzelL. YaylaM. HaliciZ. HacimuftuogluA. A review of melatonin, its receptors and drugs.Eurasian J. Med.201648213514110.5152/eurasianjmed.2015.0267 27551178
     [Google Scholar]
  26. ChauhanM. SaxenaA. SahaB. An insight in anti-malarial potential of indole scaffold: A review.Eur. J. Med. Chem.202121811340010.1016/j.ejmech.2021.113400 33823394
     [Google Scholar]
  27. LiJ.Y. SunX.F. LiJ.J. YuF. ZhangY. HuangX.J. JiangF.X. The antimalarial activity of indole alkaloids and hybrids.Arch. Pharm. (Weinheim)202035311200013110.1002/ardp.202000131 32785974
     [Google Scholar]
  28. SinghA. BhutaniC. KhannaP. TalwarS. SinghS.K. KhannaL. Recent report on indoles as a privileged anti-viral scaffold in drug discovery.Eur. J. Med. Chem.202528111701710.1016/j.ejmech.2024.117017 39509946
     [Google Scholar]
  29. HeB. HuY. MaoP. DengT. WangY. LuoX. ZouH. WangZ. XueW. Design, synthesis and antifungal activity of indole derivatives containing 1,3,4-oxadiazole.Arab. J. Chem.202417510575810.1016/j.arabjc.2024.105758
     [Google Scholar]
  30. ShenY. PanM. GaoH. ZhangY. WangR. LiJ. MaoZ. New azole derivatives linked to indole/indoline moieties combined with FLC against drug-resistant Candida albicans.RSC Medicinal Chemistry20241541236124610.1039/D4MD00021H 38665837
     [Google Scholar]
  31. JasiewiczB. Kozanecka-OkupnikW. PrzygodzkiM. WarżajtisB. RychlewskaU. PospiesznyT. MrówczyńskaL. Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives.Sci. Rep.20211111542510.1038/s41598‑021‑94904‑z 34326403
     [Google Scholar]
  32. DebM.L. BaruahP.K. BoruahA. Microwave-assisted catalyst-free hydride transfer: synthesis and evaluation of antioxidant properties of N-Benzylindolines.Synlett202410.1055/s‑0043‑1775421
     [Google Scholar]
  33. WollelaB. JemalM. Anti-HIV Drug Discovery, development and synthesis of delavirdine: Review article.IRJPAC201920116
     [Google Scholar]
  34. ChenQ. WuC. ZhuJ. LiE. XuZ. Therapeutic potential of indole derivatives as anti-HIV agents: A mini-review.Curr. Top. Med. Chem.20222212993100810.2174/1568026621666211012111901 34636313
     [Google Scholar]
  35. ReddyG.S. PalM. Indole derivatives as anti-tubercular agents: an overview on their synthesis and biological activities.Curr. Med. Chem.202128224531456810.2174/1875533XMTEwcMDkow 32951569
     [Google Scholar]
  36. BhakharK.A. SurejaD.K. DhameliyaT.M. Synthetic account of indoles in search of potential anti-mycobacterial agents: A review and future insights.J. Mol. Struct.2022124813152210.1016/j.molstruc.2021.131522
     [Google Scholar]
  37. PhillipsR.M. HendriksH.R. PetersG.J. EO9 (Apaziquone): From the clinic to the laboratory and back again.Br. J. Pharmacol.20131681111810.1111/j.1476‑5381.2012.01996.x 22509926
     [Google Scholar]
  38. LuoM.L. HuangW. ZhuH.P. PengC. ZhaoQ. HanB. Advances in indole-containing alkaloids as potential anticancer agents by regulating autophagy.Biomed. Pharmacother.202214911282710.1016/j.biopha.2022.112827 35316753
     [Google Scholar]
  39. LiS.M. Prenylated indole derivatives from fungi: Structure diversity, biological activities, biosynthesis and chemoenzymatic synthesis.Nat. Prod. Rep.2010271577810.1039/B909987P 20024094
     [Google Scholar]
  40. KumarS. Ritika, A brief review of the biological potential of indole derivatives.Future J. Pharm. Sci.20206112110.1186/s43094‑020‑00141‑y
     [Google Scholar]
  41. ShakerA.M.M. AbdelallE.K.A. AbdellatifK.R.A. Abdel-RahmanH.M. Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities.BMC Chem.20201412310.1186/s13065‑020‑00675‑5 32259135
     [Google Scholar]
  42. DebM.L. DeyS.S. BentoI. BarrosM.T. MaycockC.D. Copper-catalyzed regioselective intramolecular oxidative α-functionalization of tertiary amines: an efficient synthesis of dihydro-1,3-oxazines.Angew. Chem. Int. Ed.201352379791979510.1002/anie.201304654 23893574
     [Google Scholar]
  43. SridharanV. MenéndezJ.C. Cerium(IV) ammonium nitrate as a catalyst in organic synthesis.Chem. Rev.201011063805384910.1021/cr100004p 20359233
     [Google Scholar]
  44. PeguC.D. NasrinS.B. DebM.L. DasD.J. SaikiaK.K. BaruahP.K. CAN-catalyzed microwave promoted reaction of indole with Betti bases under solvent-free condition and evaluation of antibacterial activity of the products.Synth. Commun.201747212007201410.1080/00397911.2017.1360912
     [Google Scholar]
  45. WeiC. ZhaoL. SunZ. HuD. SongB. Discovery of novel indole derivatives containing dithioacetal as potential antiviral agents for plants.Pestic. Biochem. Physiol.202016610456810.1016/j.pestbp.2020.104568 32448422
     [Google Scholar]
  46. SongY.L. WuF. ZhangC.C. LiangG.C. ZhouG. YuJ.J. Ionic liquid catalyzed synthesis of 2-(indole-3-yl)-thiochroman-4-ones and their novel antifungal activities.Bioorg. Med. Chem. Lett.201525225926110.1016/j.bmcl.2014.11.056 25499881
     [Google Scholar]
  47. LeiZ. ChenB. KooY.M. MacFarlaneD.R. Introduction: Ionic liquids.Chem. Rev.2017117106633663510.1021/acs.chemrev.7b00246 28535681
     [Google Scholar]
  48. YaoH.C. ResnickP. Azo-hydrazone conversion. I. The Japp-Klingemann reaction.J. Am. Chem. Soc.196284183514351710.1021/ja00877a018
     [Google Scholar]
  49. Cihan-ÜstündağG. NaesensL. ŞatanaD. Erköse-GençG. Mataracı-KaraE. ÇapanG. Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives.Monatsh. Chem.201915081533154410.1007/s00706‑019‑02457‑9 32214484
     [Google Scholar]
  50. YousifM.N. HusseinH.A. YousifN.M. El-ManawatyM.A. El-SayedW.A. Synthesis and anticancer activity of novel 2-phenylindole linked imidazolothiazole, thiazolo-s-triazine and imidazolyl-sugar systems.J. Appl. Pharm. Sci.20199161410.7324/JAPS.2019.90102
     [Google Scholar]
  51. VasconcelosS.N.S. MeissnerK.A. FerrazW.R. TrossiniG.H.G. WrengerC. StefaniH.A. Indole-3-glyoxyl tyrosine: Synthesis and antimalarial activity against Plasmodium falciparum.Future Med. Chem.201911652553810.4155/fmc‑2018‑0246 30916995
     [Google Scholar]
  52. IsmailM.M. KamelM.M. MohamedL.W. FaggalS.I. Synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors.Molecules20121754811482310.3390/molecules17054811 22534665
     [Google Scholar]
  53. Gurkan-AlpA.S. MumcuogluM. AndacC.A. DayancE. Cetin-AtalayR. BuyukbingolE. Synthesis, anticancer activities and molecular modeling studies of novel indole retinoid derivatives.Eur. J. Med. Chem.20125834635410.1016/j.ejmech.2012.10.013 23142674
     [Google Scholar]
  54. HongW. LiJ. ChangZ. TanX. YangH. OuyangY. YangY. KaurS. PatersonI.C. NgeowY.F. WangH. Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens.J. Antibiot. (Tokyo)201770783284410.1038/ja.2017.55 28465626
     [Google Scholar]
  55. AgrawalK. PatelT. PatelR. Synthesis, biological activity of newly designed sulfonamide based indole derivative as anti-microbial agent.Future J. Pharm. Sci.2023911710.1186/s43094‑023‑00466‑4
     [Google Scholar]
  56. HanX. WuH. WangW. DongC. TienP. WuS. ZhouH.B. Synthesis and SARs of indole-based α-amino acids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.Org. Biomol. Chem.201412418308831710.1039/C4OB01333F 25209054
     [Google Scholar]
  57. GaurA. PeerzadaM.N. KhanN.S. AliI. AzamA. Synthesis and anticancer evaluation of novel indole based arylsulfonylhydrazides against human breast cancer cells.ACS Omega2022746420364204310.1021/acsomega.2c03908 36440122
     [Google Scholar]
  58. ShaikhT.M.A. DebebeH. Synthesis and evaluation of antimicrobial activities of novel N‐substituted indole derivatives.J. Chem.202020204358453
     [Google Scholar]
  59. HawashM. KahramanD.C. ErgunS.G. Cetin-AtalayR. BaytasS.N. Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines.BMC Chem.20211516610.1186/s13065‑021‑00793‑8 34930409
     [Google Scholar]
  60. Al-WahaibiL.H. Abou-ZiedH.A. AbdelrahmanM.H. MorcossM.M. TrembleauL. YoussifB.G.M. BräseS. Design and synthesis new indole-based aromatase/iNOS inhibitors with apoptotic antiproliferative activity.Front Chem.202412143292010.3389/fchem.2024.1432920 39308851
     [Google Scholar]
/content/journals/coc/10.2174/0113852728382848250610051815
Loading
Insights into the Synthesis and Bioactivity of Indole-Based Compounds: A Short Review
Current Organic Chemistry 30, 285 (2026); https://doi.org/10.2174/0113852728382848250610051815
/content/journals/coc/10.2174/0113852728382848250610051815
/content/journals/coc/10.2174/0113852728382848250610051815
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): heterocycles; Indole derivatives; melatonin; pharmacological properties; structure-activity relationship; synthetic strategies

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