Skip to content
2000
Volume 29, Issue 18
  • ISSN: 1385-2728
  • E-ISSN: 1875-5348

Abstract

Heterocyclic scaffolds, particularly indole and thiazole compounds, are revolutionizing the treatment of lung diseases due to their structural diversity and broad therapeutic potential. Their ability to target multiple biological pathways positions them as powerful tools for developing innovative treatments for lung disorders, particularly lung cancer. This review systematically explores recent advances in the synthesis and biological evaluation of indole and thiazole derivatives, emphasizing detailed synthetic strategies and the identification of the most potent molecules reported in the studies referenced within this manuscript for their relevance to lung diseases, particularly lung cancer. The SAR studies elucidate the role of molecular features and key functional groups in enhancing the potency, selectivity, and therapeutic efficacy of synthetic indole and thiazole derivatives. Given that lung cancer remains the leading cause of cancer-related deaths worldwide, the findings highlight the urgent need for developing innovative and effective anti-lung cancer agents, with indole and thiazole scaffolds serving as promising therapeutic frameworks.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/coc/10.2174/0113852728363709250208183711
2025-02-20
2025-09-27

  • From This Site

    /content/journals/coc/10.2174/0113852728363709250208183711
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AchesonR.M. Reactions of acetylenecarboxylic acids and their esters with nitrogen-containing heterocyclic compounds.Adv. Heterocycl. Chem.1963112516510.1016/S0065‑2725(08)60524‑3 14087219
     [Google Scholar]
  2. BrackW. SchirmerK. Effect-directed identification of oxygen and sulfur heterocycles as major polycyclic aromatic cytochrome P4501A-inducers in a contaminated sediment.Environ. Sci. Technol.200337143062307010.1021/es020248j 12901651
     [Google Scholar]
  3. PadwaA. BurS.K. The domino way to heterocycles.Tetrahedron200763255341537810.1016/j.tet.2007.03.158 17940591
     [Google Scholar]
  4. McGrathN.A. BrichacekM. NjardarsonJ.T. A graphical journey of innovative organic architectures that have improved our lives.J. Chem. Educ.2010871210.1021/ed1003806
     [Google Scholar]
  5. GomtsyanA. Heterocycles in drugs and drug discovery.Chem. Heterocycl. Comp.20124871010.1007/s10593‑012‑0960‑z
     [Google Scholar]
  6. MinickaitėR. GrybaitėB. VaickelionienėR. KavaliauskasP. PetraitisV. PetraitienėR. TumosienėI. JonuškienėI. MickevičiusV. Synthesis of novel aminothiazole derivatives as promising antiviral, antioxidant and antibacterial candidates.Int. J. Mol. Sci.20222314768810.3390/ijms23147688 35887038
     [Google Scholar]
  7. DorababuA. Indole a promising pharmacophore in recent antiviral drug discovery.RSC Med. Chem.20201112133510.1039/D0MD00288G
     [Google Scholar]
  8. RakeshK.P. KumaraH.K. UllasB.J. ShivakumaraJ. Channe GowdaD. Amino acids conjugated quinazolinone-Schiff’s bases as potential antimicrobial agents: Synthesis, SAR and molecular docking studies.Bioorg. Chem.20199010309310.1016/j.bioorg.2019.103093 31288137
     [Google Scholar]
  9. QinH.L. LiuJ. FangW.Y. RavindarL. RakeshK.P. Indole-based derivatives as potential antibacterial activity against methicillin-resistance Staphylococcus aureus (MRSA).Eur. J. Med. Chem.202019411224510.1016/j.ejmech.2020.112245
     [Google Scholar]
  10. JatavV. MishraP. KashawS. StablesJ.P. Synthesis and CNS depressant activity of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quina-zoline-4(3H)-ones.Eur. J. Med. Chem.200843113514110.1016/j.ejmech.2007.02.004 17418452
     [Google Scholar]
  11. KumarR.R. KumarV. KaurD. NandiN.K. DwivediA.R. KumarV. KumarB. Investigation of indole‐3‐piperazinyl derivatives as potential antidepressants: Design, synthesis, in vitro, in vivo and in silico analysis.ChemistrySelect2021641112761128410.1002/slct.202103568
     [Google Scholar]
  12. SinghT.P. SinghO.M. Recent progress in biological activities of indole and indole alkaloids.Mini Rev. Med. Chem.201718192510.2174/1389557517666170807123201 28782480
     [Google Scholar]
  13. ArshadM.F. AlamA. AlshammariA.A. AlhazzaM.B. AlzimamI.M. AlamM.A. MustafaG. AnsariM.S. AlotaibiA.M. AlotaibiM.M. Thiazole: A versatile standalone moiety contributing to the development of various drugs and biologically active agents.Molecules20222713399410.3390/molecules27133994
     [Google Scholar]
  14. 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
     [Google Scholar]
  15. MasoudiniaS. SamadizadehM. SafaviM. BijanzadehH.R. ForoumadiA. Novel quinazolines bearing 1,3,4-thiadiazole-aryl urea derivative as anticancer agents: Design, synthesis, molecular docking, DFT and bioactivity evaluations.BMC Chem.20241813010.1186/s13065‑024‑01119‑0 38347613
     [Google Scholar]
  16. AkhtarJ. KhanA.A. AliZ. HaiderR. Shahar YarM. Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities.Eur. J. Med. Chem.201712514318910.1016/j.ejmech.2016.09.023 27662031
     [Google Scholar]
  17. NiuZ.X. WangY.T. ZhangS.N. LiY. ChenX.B. WangS.Q. LiuH.M. Application and synthesis of thiazole ring in clinically approved drugs.Eur. J. Med. Chem.202325011517211517210.1016/j.ejmech.2023.115172 36758304
     [Google Scholar]
  18. PunV.C. KazemiparkouhiF. ManjouridesJ. Suh ScdH.H. SuhH.H. ProfessorD. Long-Term PM2.5 exposure and respiratory, cancer, and cardiovascular mortality in older US adults.Am. J. Epidemiol.2017186896110.1093/aje/kwx166
     [Google Scholar]
  19. KruegerG.R.F. WagnerM. OldhamS.A.A. Pathology of the Respiratory Tract.Atlas of Anatomic Pathology with Imaging.LondonSpringer London201310518910.1007/978‑1‑4471‑2846‑5_3
     [Google Scholar]
  20. RabeK.F. WatzH. Chronic obstructive pulmonary disease.Lancet20173891931194010.1016/S0140‑6736(17)31222‑9
     [Google Scholar]
  21. AlcónA. FàbregasN. TorresA. Pathophysiology of pneumonia.Clin. Chest Med.20052663910.1016/j.ccm.2004.10.013
     [Google Scholar]
  22. CheungW.K.C. NguyenD.X. Lineage factors and differentiation states in lung cancer progression.Oncogene20153447577110.1038/onc.2015.85
     [Google Scholar]
  23. SealeD.D. BeaverB.M. Pathophysiology of lung cancer.Nurs. Clin. North Am.199227360361310.1016/S0029‑6465(22)02790‑6 1508734
     [Google Scholar]
  24. LandiM.T. SynnottN.C. RosenbaumJ. ZhangT. ZhuB. ShiJ. ZhaoW. KebedeM. SangJ. ChoiJ. MendozaL. PachecoM. HicksB. CaporasoN.E. AbubakarM. GordeninD.A. WedgeD.C. AlexandrovL.B. RothmanN. LanQ. Garcia-ClosasM. ChanockS.J. Tracing lung cancer risk factors through mutational signatures in never-smokers.Am. J. Epidemiol.2021190696297610.1093/aje/kwaa234 33712835
     [Google Scholar]
  25. HarkerJ.A. LloydC.M. T helper 2 cells in asthma.J. Exp. Med.20232206e2022109410.1084/jem.20221094
     [Google Scholar]
  26. ZhuX. CuiJ. YiL. QinJ. TulakeW. TengF. TangW. WeiY. DongJ. The role of T cells and macrophages in asthma pathogenesis: A new perspective on mutual crosstalk.Mediators Inflamm.2020202011410.1155/2020/7835284 32922208
     [Google Scholar]
  27. SundarI.K. YaoH. RahmanI. Oxidative stress and chromatin remodeling in chronic obstructive pulmonary disease and smoking-related diseases.Antioxid. Redox Signal.20131815195610.1089/ars.2012.4863
     [Google Scholar]
  28. MacneeW. Pathogenesis of chronic obstructive pulmonary diseaseProc Am Thorac Soc20052425810.1513/pats.200504‑045SR
     [Google Scholar]
  29. MaisonD.P. Tuberculosis pathophysiology and anti-VEGF intervention Clin.Tuberc. Other Mycobact. Dis.20222710030010.1016/j.jctube.2022.100300
     [Google Scholar]
  30. GazdarA.F. ShigematsuH. HerzJ. MinnaJ.D. Mutations and addiction to EGFR: The Achilles ‘heal’ of lung cancers?Trends Mol. Med.2004101048148610.1016/j.molmed.2004.08.008 15464447
     [Google Scholar]
  31. BurgeS. WedzichaJ.A. COPD exacerbations: Definitions and classifications.Eur. Respir. J. Suppl.20034146s10.1183/09031936.03.00078002
     [Google Scholar]
  32. HalwaniR. Al-MuhsenS. HamidQ. T helper 17 cells in airway diseases: From laboratory bench to bedside.Chest2013143249450110.1378/chest.12‑0598 23381314
     [Google Scholar]
  33. BarnesP.J. Cellular and molecular mechanisms of asthma and COPD.Clin. Sci. (Lond.)2017131131541155810.1042/CS20160487
     [Google Scholar]
  34. AdlerV. YinZ. RonaiZ. TewK.D. Role of redox potential and reactive oxygen species in stress signaling.Oncogene1999186104611110.1038/sj.onc.1203128
     [Google Scholar]
  35. RahmanI. MacneeW. Role of transcription factors in inflammatory lung diseases.Thorax199853760110.1136/thx.53.7.601
     [Google Scholar]
  36. LiuY. KongH. CaiH. ChenG. ChenH. RuanW. Progression of the PI3K/Akt signaling pathway in chronic obstructive pulmonary disease.Front. Pharmacol.202314123878210.3389/fphar.2023.1238782
     [Google Scholar]
  37. SethiS. Infectious etiology of acute exacerbations of chronic bronchitis.Chest20001175Suppl. 2380S385S10.1378/chest.117.5_suppl_2.380S 10843981
     [Google Scholar]
  38. GosensR. HiemstraP.S. AdcockI.M. BrackeK.R. DicksonR.P. HansbroP.M. Krauss-EtschmannS. SmitsH.H. StassenF.R.M. BartelS. Host-microbe cross-talk in the lung microenvironment: Implications for understanding and treating chronic lung disease.Eur. Respir. J.2020562190232010.1183/13993003.02320‑2019 32430415
     [Google Scholar]
  39. BallesterB. MilaraJ. CortijoJ. Idiopathic pulmonary fibrosis and lung cancer: Mechanisms and molecular targets.Int. J. Mol. Sci.201920359310.3390/ijms20030593
     [Google Scholar]
  40. WangJ. HuK. CaiX. YangB. HeQ. WangJ. WengQ. Targeting PI3K/Akt signaling for treatment of idiopathic pulmonary fibrosis.Acta Pharm. Sin. B202212183210.1016/j.apsb.2021.07.023
     [Google Scholar]
  41. Martín-MedinaA. Cerón-PisaN. Martinez-FontE. ShafiekH. Obrador-HeviaH. SauledaJ. IglesiasA. TLR/WNT: A novel relationship in immunomodulation of lung cancer.Int. J. Mol. Sci.20222312653910.3390/ijms23126539
     [Google Scholar]
  42. StellaG.M. D’AgnanoV. PiloniD. SaracinoL. LettieriS. MarianiF. LanciaA. BortolottoC. RinaldiP. The oncogenic landscape of the idiopathic pulmonary fibrosis: A narrative review.Transl. Lung Cancer Res.20221147249610.21037/tlcr‑21‑880
     [Google Scholar]
  43. GeL. HuQ. ShiM. YangH. ZhuG. Design and discovery of novel thiazole derivatives as potential MMP inhibitors to protect against acute lung injury in sepsis rats via attenuation of inflammation and apoptotic oxidative stress.RSC Advances2017752329093292210.1039/C7RA03511J
     [Google Scholar]
  44. LinZ. WangZ. ZhouX. ZhangM. GaoD. ZhangL. WangP. ChenY. LinY. ZhaoB. MiaoJ. KongF. Discovery of new fluorescent thiazole-pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells.Cell Death Dis.202011755110.1038/s41419‑020‑02746‑w 32686662
     [Google Scholar]
  45. SharmaA. SharmaD. SainiN. SharmaS.V.V. ThakurV.K. Recent advances in synthetic strategies and SAR of thiazolidin-4-one containing molecules in cancer therapeutics.Cancer Metastasis Rev.202342384710.1007/s10555‑023‑10106‑1
     [Google Scholar]
  46. EvrenA.E. YurttasL. EkselliB. Akalin-CiftciG. Synthesis and biological evaluation of 5-methyl-4-phenyl thiazole derivatives as anticancer agents.Phosphorus Sulfur Silicon Relat. Elem.2019194882082810.1080/10426507.2018.1550642
     [Google Scholar]
  47. SharmaP. Srinivasa ReddyT. ThummuriD. SenwarK.R. Praveen KumarN. NaiduV.G.M. BhargavaS.K. ShankaraiahN. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents.Eur. J. Med. Chem.201612460862110.1016/j.ejmech.2016.08.029 27614408
     [Google Scholar]
  48. SharmaP. ReddyT.S. KumarN.P. SenwarK.R. BhargavaS.K. ShankaraiahN. Conventional and microwave-assisted synthesis of new 1 H -benzimidazole-thiazolidinedione derivatives: A potential anticancer scaffold.Eur. J. Med. Chem.201713823424510.1016/j.ejmech.2017.06.035 28668476
     [Google Scholar]
  49. Turan-ZitouniG. AltıntopM.D. ÖzdemirA. KaplancıklıZ.A. ÇiftçiG.A. TemelH.E. Synthesis and evaluation of bis-thiazole derivatives as new anticancer agents.Eur. J. Med. Chem.201610728829410.1016/j.ejmech.2015.11.002 26599534
     [Google Scholar]
  50. HavrylyukD. MosulaL. ZimenkovskyB. VasylenkoO. GzellaA. LesykR. Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety.Eur. J. Med. Chem.201045115012502110.1016/j.ejmech.2010.08.008 20810193
     [Google Scholar]
  51. FuP.K. YangC.Y. HuangS.C. HungY.W. JengK.C. HuangY.P. ChuangH. HuangN.C. LiJ.P. HsuM.H. ChenJ.K. Evaluation of LPS-induced acute lung injury attenuation in rats by aminothiazole-paeonol derivatives.Molecules20172210160510.3390/molecules22101605 28946699
     [Google Scholar]
  52. PesceE. PedemonteN. LeoniA. LocatelliA. MorigiR. Synthesis and biological evaluation of thiazole derivatives on basic defects underlying cystic fibrosis.Bioorg. Med. Chem. Lett.2020302112747310.1016/j.bmcl.2020.127473 32784089
     [Google Scholar]
  53. AshmawyF.O. GomhaS.M. AbdallahM.A. ZakiM.E.A. Al-HussainS.A. El-desoukyM.A. Synthesis, in vitro evaluation and molecular docking studies of novel thiophenyl thiazolyl-pyridine hybrids as potential anticancer agents.Molecules20232811427010.3390/molecules28114270 37298747
     [Google Scholar]
  54. SondhiS.M. RaniR. GuptaP.P. AgrawalS.K. SaxenaA.K. Synthesis, anticancer, and anti-inflammatory activity evaluation of methanesulfonamide and amidine derivatives of 3,4-diaryl-2-imino-4-thiazolines.Mol. Divers.200913335736610.1007/s11030‑009‑9125‑0 19267213
     [Google Scholar]
  55. ChenT. WeiY. ZhuG. ZhaoH. ZhangX. Design, synthesis and structure-activity relationship studies of 4- indole-2-arylaminopyrimidine derivatives as anti-inflammatory agents for acute lung injury.Eur. J. Med. Chem.202022511376610.1016/j.ejmech.2021.113766
     [Google Scholar]
  56. ZhengZ. LiX. ChenP. ZouY. ShiX. LiX. Young KimE. LiaoJ. YangJ. ChattipakornN. WuG. TangQ. ChoW.J. LiangG. Design and synthesis optimization of novel diimide indoles derivatives for ameliorating acute lung injury through modulation of NF-κB signaling pathway.Bioorg. Chem.202313610655710.1016/j.bioorg.2023.106557 37121106
     [Google Scholar]
  57. OffermanS.C. KadirvelM. AbusaraO.H. BryantJ.L. TelferB.A. BrownG. FreemanS. WhiteA. WilliamsK.J. AojulaH.S. N-tert-Prenylation of the indole ring improves the cytotoxicity of a short antagonist G analogue against small cell lung cancer.MedChemComm20178355155810.1039/C6MD00691D 30108771
     [Google Scholar]
  58. Haitham AbusaraO. FreemanS. AojulaH.S. Pentapeptides for the treatment of small cell lung cancer: Optimisation by N ind -alkyl modification of the tryptophan side chain.Eur. J. Med. Chem.201713722123210.1016/j.ejmech.2017.05.053 28595067
     [Google Scholar]
  59. Manuel-ManresaP. Korrodi-GregórioL. HernandoE. VillanuevaA. Martínez-GarcíaD. RodillaA.M. RamosR. FardilhaM. MoyaJ. QuesadaR. Soto-CerratoV. Pérez-TomásR. Novel indole-based tambjamine-analogues induce apoptotic lung cancer cell death through p38 mitogen-activated protein kinase activation.Mol. Cancer Ther.20171671224123510.1158/1535‑7163.MCT‑16‑0752 28396364
     [Google Scholar]
  60. GuJ. YuanY. YangQ. ZhengP.F. ShanC. WangF. ChenX.H. OuyangQ. Discovery of a pyrano[2,3-b]pyridine derivative YX-2102 as a cannabinoid receptor 2 agonist for alleviating lung fibrosis.Eur. J. Med. Chem.202220156510.1186/s12967‑022‑03773‑1
     [Google Scholar]
  61. DhuguruJ. SkoutaR. Role of indole scaffolds as pharmacophores in the development of anti-lung cancer agents.Molecules2020257161510.3390/molecules25071615 32244744
     [Google Scholar]
  62. SongZ. ZhouY. ZhangW. ZhanL. YuY. ChenY. JiaW. LiuZ. QianJ. ZhangY. LiC. LiangG. Base promoted synthesis of novel indole-dithiocarbamate compounds as potential anti-inflammatory therapeutic agents for treatment of acute lung injury.Eur. J. Med. Chem.2019171546510.1016/j.ejmech.2019.03.022 30909020
     [Google Scholar]
  63. GaikwadR. BobdeY. GaneshR. PatelT. RathoreA. GhoshB. DasK. GayenS. 2-Phenylindole derivatives as anticancer agents: ynthesis and screening against murine melanoma, human lung and breast cancer cell lines.Synth. Commun.201949172258226910.1080/00397911.2019.1620282
     [Google Scholar]
  64. LimH.M. ParkS.H. NamM.J. Induction of apoptosis in indole-3-carbinol-treated lung cancer H1299 cells via ROS level elevation.Hum. Exp. Toxicol.202140581282510.1177/0960327120969968 33118390
     [Google Scholar]
  65. IslamM.I. SeoH. KimS. SaduV.S. LeeK.I. SongH.Y. Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosis.Sci. Rep.202111174010.1038/s41598‑020‑80227‑y 33436895
     [Google Scholar]
  66. RameshD. JojiA. VijayakumarB.G. SethumadhavanA. ManiM. KannanT. Indole chalcones: Design, synthesis, in vitro and in silico evaluation against Mycobacterium tuberculosis.Eur. J. Med. Chem.202019811235810.1016/j.ejmech.2020.112358 32361610
     [Google Scholar]
  67. LiL. MaL. WangD. JiaH. YuM. GuY. ShangH. ZouZ. Design and synthesis of matrine derivatives as novel anti-pulmonary fibrotic agents via repression of the TGFβ/Smad pathway.Molecules2019246110810.3390/molecules24061108 30897818
     [Google Scholar]
/content/journals/coc/10.2174/0113852728363709250208183711
Loading
Unveiling the Therapeutic Promise of Indole and Thiazole Derivatives in Treating Lung Diseases
Current Organic Chemistry 29, 1440 (2025); https://doi.org/10.2174/0113852728363709250208183711
/content/journals/coc/10.2174/0113852728363709250208183711
/content/journals/coc/10.2174/0113852728363709250208183711
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): heterocyclic compounds; indole; lung cancer; Lung diseases; SAR studies; thiazole

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