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Volume 23, Issue 4
  • ISSN: 1871-5230
  • E-ISSN:

Abstract

Background

A series of novel 2-(isoquinolin-1-yl)-spiro[oxindole-3,3′-pyrrolines] were synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 3-phenylimidazo[5,1-]isoquinoline and -alkylisatins in chloroform at ∼60°C for 24 h.

Aims

This study aimed at the synthesis of novel spirooxindole-3,3'-pyrrolines derivatives and evaluation of cytotoxicity affinities in cross-correlations with their anti-inflammation and radical scavenging capacities.

Objectives

The objective of this study was to use a one-pot, three-component reaction to synthesize a novel set of spirooxindole-3,3'-pyrrolines derivatives.

Methods

A novel set of spirooxindole-3,3'-pyrrolines () was synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 3-phenylimidazo[5,1-]isoquinoline and -alkylisatins in chloroform at ∼60°C for 24 h. These new compounds were characterized by 1HNMR, 13C-NMR, and HRMS spectral data and screened for their antitumor, anti-inflammatory, antibacterial, antifungal, and antioxidant activities.

Results

The new synthetic spirooxindole-3,3'-pyrrolines ()-tested compounds displayed significant anti-inflammatory properties and were noncytotoxic on PDL fibroblasts. However, they lacked antioxidative-DPPH radical scavenging capabilities. Notably, Doxorubicin and cisplatin demonstrated antiproliferative effects on various cancer monolayers. Moreover, compounds , , , , and exhibited pronounced viability reduction properties in colorectal and pancreatic cancer monolayers, as well as across skin, lung, prostate, and cervical adenocarcinomas, with higher cytotoxicity in mammary cancer cells MCF7 and T47D. None of the tested compounds had significant antibacterial activity against or . However, compounds , , and exhibited notable antifungal properties, indicating potential for further investigation.

Conclusion

Eight new synthetic spiro[indoline-3,3-pyrroles] were prepared, characterized, and evaluated for their anti-inflammatory and cytotoxic properties. The compounds showed significant anti-inflammatory effects and promising cytotoxicity against various cancer monolayers, especially in colorectal and pancreatic cancers. Some compounds also exhibited antifungal properties. However, they did not exhibit significant antibacterial activity.

© 2024 Bentham Science Publishers
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2024-07-25
2024-11-22

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References

  1. SahaS.K. LeeS.B. WonJ. ChoiH.Y. KimK. YangG.M. DayemA.A. ChoS. Correlation between oxidative stress, nutrition, and cancer initiation.Int. J. Mol. Sci.2017187154410.3390/ijms18071544
     [Google Scholar]
  2. KlaunigJ.E. Oxidative stress and cancer.Curr. Pharm. Des.201924404771477810.2174/1381612825666190215121712
     [Google Scholar]
  3. ZahraK.F. LefterR. AliA. AbdellahE-C. TrusC. CiobicaA. TimofteD. The involvement of the oxidative stress status in cancer pathology: A double view on the role of the antioxidants.Oxid. Med. Cell. Longev.20212021996591610.1155/2021/9965916
     [Google Scholar]
  4. WangD. DuBoisR.N. The role of COX-2 in intestinal inflammation and colorectal cancer.Oncogene201029678178810.1038/onc.2009.421
     [Google Scholar]
  5. Haj HusseinB. KasabriV. Al-HiariY. ArabiyatS. IkhmaisB. AlalawiS. Al-QirimT. Selected statins as dual antiproliferative-antiinflammatory compounds.Asian Pac. J. Cancer Prev.202223124047406210.31557/APJCP.2022.23.12.4047
     [Google Scholar]
  6. ZhangY. PuW. BousquenaudM. CattinS. ZaricJ. SunL. RüeggC. Emodin inhibits inflammation, carcinogenesis, and cancer progression in the AOM/DSS model of colitis-associated intestinal tumorigenesis.Front. Oncol.20211056467410.3389/fonc.2020.564674
     [Google Scholar]
  7. GretenF.R. GrivennikovS.I. Inflammation and cancer: Triggers, mechanisms, and consequences.Immunity2019511274110.1016/j.immuni.2019.06.025
     [Google Scholar]
  8. XiongS. DongL. ChengL. Neutrophils in cancer carcinogenesis and metastasis.J. Hematol. Oncol.202114117310.1186/s13045‑021‑01187‑y
     [Google Scholar]
  9. NairV. DeepthiA. AshokD. RaveendranA.E. PaulR.R. 1,4-Dipolar cycloadditions and related reactions.Tetrahedron201470193085310510.1016/j.tet.2014.03.014
     [Google Scholar]
  10. JaberA.M. ZahraJ.A. SabriS.S. KhanfarM.A. AwwadiF.F. El-AbadelahM.M. New trends in 1,4-dipolar cycloaddition reactions. thermodynamic control synthesis of model 2′-(isoquinolin-1-yl)-spiro.[oxindole-3,3′-pyrrolines] Curr. Org. Chem. 202226554254910.2174/1385272826666220221141306
     [Google Scholar]
  11. PavlovskaT.L. RedkinR.G. LipsonV.V. AtamanukD.V. Molecular diversity of spirooxindoles. Synthesis and biological activity.Mol. Divers.201620129934410.1007/s11030‑015‑9629‑8
     [Google Scholar]
  12. SaraswatP. JeyabalanG. HassanM.Z. RahmanM.U. NyolaN.K. Review of synthesis and various biological activities of spiro heterocyclic compounds comprising oxindole and pyrrolidine moities.Synth. Commun.201646201643166410.1080/00397911.2016.1211704
     [Google Scholar]
  13. AniD. NobleV. VidyaS. Green protocols for the synthesis of 3, 3′-spirooxindoles-2016-mid 2019.Curr. Green Chem.2019621022510.2174/2213346106666191019144116
     [Google Scholar]
  14. MaiuoloL. AlgieriV. OlivitoF. De NinoA. Recent developments on 1, 3-dipolar cycloaddition reactions by catalysis in green solvents.Catalysts2020106592
     [Google Scholar]
  15. SaranyaP.V. NeethaM. AneejaT. AnilkumarG. Transition metal-catalyzed synthesis of spirooxindoles.RSC Advances202111137146717910.1039/D1RA00139F
     [Google Scholar]
  16. Auria-LunaF. Marqués-LópezE. MohammadiS. HeiranR. HerreraR. New organocatalytic asymmetric synthesis of highly substituted chiral 2-oxospiro-[indole-3, 4′-(1′, 4′-dihydropyridine)] derivatives.Molecules2015209158071582610.3390/molecules200915807
     [Google Scholar]
  17. BanerjeeP. PandeyA.K. Synthesis of functionalized dispiro-oxindoles through azomethine ylide dimerization and mechanistic studies to explain the diastereoselectivity.RSC Advances2014463332363324410.1039/C4RA01492H
     [Google Scholar]
  18. HuisgenR. MorikawaM. HerbigK. BrunnE. 1.4‐Dipolare Cycloadditionen, II. Dreikomponenten‐Reaktionen des Isochinolins mit Acetylendicarbonsäureester und verschiedenen Dipolarophilen.Chem. Ber.196710041094110610.1002/cber.19671000406
     [Google Scholar]
  19. Al-MahadeenM.M. ZahraJ.A. El-AbadelahM.M. JaberA.M. KhanfarM.A. One-pot synthesis of novel 2-oxo(2H)-spiro[benzofuran-3,3′-pyrrolines] via 1,4-dipolar cycloaddition reaction.Results in Chemistry2022410064310.1016/j.rechem.2022.100643
     [Google Scholar]
  20. JaberA.M. ZahraJ.A. El-AbadelahM.M. SabriS.S. KhanfarM.A. VoelterW. Utilization of 1-phenylimidazo[1,5- a]quinoline as partner in 1,4-dipolar cycloaddition reactions.Z. Naturforsch. B. J. Chem. Sci.202075325926710.1515/znb‑2019‑0150
     [Google Scholar]
  21. JaberA.M. ZahraJ.A. El-AbadelahM.M. SabriS.S. SabbahD.S. Thermodynamic control synthesis of spiro[oxindole-3,3′-pyrrolines] via 1,4-dipolar cycloaddition utilizing imidazo[1,5- a]quinoline.Z. Naturforsch. C J. Biosci.2023783-414114810.1515/znc‑2022‑0085
     [Google Scholar]
  22. El-FahamA. HozzeinW.N. WadaanM.A. KhattabS.N. GhabbourH.A. FunH-K. SiddiquiM.R. Microwave synthesis, characterization, and antimicrobial activity of some novel isatin derivatives.J. Chem.2015201571698710.1155/2015/716987
     [Google Scholar]
  23. BeauchardA. FerandinY. FrèreS. LozachO. BlairvacqM. MeijerL. ThiéryV. BessonT. Synthesis of novel 5-substituted indirubins as protein kinases inhibitors.Bioorg. Med. Chem.200614186434644310.1016/j.bmc.2006.05.036
     [Google Scholar]
  24. WangY. ChengX. ZhanZ. MaX. NieR. HaiL. WuY. IBX-promoted domino reaction of α-hydroxy amides: A facile one-pot synthesis of isatins.RSC Advances2016642870287410.1039/C5RA25036F
     [Google Scholar]
  25. JiangH. HuQ. CaiJ. CuiZ. ZhengJ. ChenW. Synthesis and dyeing properties of indophenine dyes for polyester fabrics.Dyes Pigments201916613013910.1016/j.dyepig.2019.03.025
     [Google Scholar]
  26. BuxtonC.S. BlakemoreD.C. BowerJ.F. Reductive coupling of acrylates with ketones and ketimines by a nickel‐catalyzed transfer‐hydrogenative strategy.Angew. Chem. Int. Ed.20175644138241382810.1002/anie.201707531
     [Google Scholar]
  27. WangQ. ZhangS. GuoF. ZhangB. HuP. WangZ.J.T.J.o.O.C. Natural α-amino acids applied in the synthesis of imidazo[1,5-a]N-heterocycles under mild conditions.J. Org. Chem.201277241116111166
     [Google Scholar]
  28. KaurG. DufourJ.M.J.S. Cell lines: Valuable tools or useless artifacts; Taylor & Francis: Milton Park, in Oxfordshire, 2012215
     [Google Scholar]
  29. ShehadiI.A. DelmaniF.A. JaberA.M. HammadH. AlDamenM.A. Al-QawasmehR.A. KhanfarM.A. Synthesis, characterization and biological evaluation of metal adamantyl 2-pyridylhydrazone complexes.Molecules20202511253010.3390/molecules25112530
     [Google Scholar]
  30. Al-NuaimiA. Al-HiariY. KasabriV. HaddadinR. MamdoohN. AlalawiS. KhaleelS. A novel class of functionalized synthetic fluoroquinolones with dual antiproliferative - antimicrobial capacities.Asian Pac. J. Cancer Prev.20212241075108610.31557/APJCP.2021.22.4.1075
     [Google Scholar]
  31. IbrahimR. KasabriV. SunoqrotS. ShalabiD. AlkhateebR. AlhiariY. Preparation and characterization of rutin-encapsulated polymeric micelles and studies of synergism with bioactive benzoic acids and triazolofluoroquinolones as anticancer nanomedicines.Asian Pac. J. Cancer Prev.202324397798910.31557/APJCP.2023.24.3.977
     [Google Scholar]
  32. ShamsheerR. SunoqrotS. KasabriV. ShalabiD. AlkhateebR. AlhiariY. AbabnehR. IkhmaisB. AbumansourH. Preparation and characterization of capsaicin encapsulated polymeric micelles and studies of synergism with nicotinic acids as potential anticancer nanomedicines.J. Pharm. Bioallied Sci.202315310712510.4103/jpbs.jpbs_311_22
     [Google Scholar]
  33. PiazziniV. D’AmbrosioM. LuceriC. CinciL. LanducciE. BiliaA.R. BergonziM.C. Formulation of nanomicelles to improve the solubility and the oral absorption of silymarin.Molecules2019249168810.3390/molecules24091688
     [Google Scholar]
  34. WolfL.J. StinguC.S. Antimicrobial susceptibility profile of rare anaerobic bacteria.Antibiotics 20221216310.3390/antibiotics12010063
     [Google Scholar]
  35. JørgensenK.M. AstvadK.M.T. HareR.K. ArendrupM.C. EUCAST susceptibility testing of isavuconazole: MIC data for contemporary clinical mold and yeast isolates.Antimicrob. Agents Chemother.2019636e00073e1910.1128/AAC.00073‑19
     [Google Scholar]
  36. BerkowE.L. LockhartS.R. Ostrosky-ZeichnerL. Antifungal susceptibility testing: Current approaches.Clin. Microbiol. Rev.2020333e00069e1910.1128/CMR.00069‑19
     [Google Scholar]
  37. El-HamolyT. El-SharawyD.M. El RefayeM.S. Abd El-RahmanS.S. L-thyroxine modifies nephrotoxicity by regulating the apoptotic pathway: The possible role of CD38/ADP-ribosyl cyclase-mediated calcium mobilization.PLoS One2017129e018415710.1371/journal.pone.0184157
     [Google Scholar]
  38. KasabriV. KhaleelS. Al-HiariY. HaddadinR. AlbashitiR. Al-ZweriM. BustanjiY. Antiproliferative Properties of 7,8-Ethylene Diamine Chelator-Lipophilic Fluoroquinolone Derivatives Against Colorectal Cancer Cell Lines.Anticancer. Agents Med. Chem.20222251012102810.2174/1871520621666210623111744
     [Google Scholar]
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Evaluation of Spirooxindole-3,3'-pyrrolines-incorporating Isoquinoline Motif as Antitumor, Anti-inflammatory, Antibacterial, Antifungal, and Antioxidant Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) 23, 261 (2024); https://doi.org/10.2174/0118715230322113240705071750
/content/journals/aiaamc/10.2174/0118715230322113240705071750
/content/journals/aiaamc/10.2174/0118715230322113240705071750
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  • Article Type:     Research Article
Keyword(s): 3-Phenylimidazo[5,1-a]isoquinoline; antioxidant activities; cascade reactions; dimethyl acetylenedicarboxylate; N-Alkylisatins; spirooxindole-3,3'-pyrrolines

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