Skip to content
2000
Volume 12, Issue 3
  • ISSN: 2213-3372
  • E-ISSN: 2213-3380

Abstract

Aims and Objectives

The study aimed to employ one-pot solvent-free boric acid-catalyzed multicomponent reactions (MCRs) to synthesize bioactive thioamidoalkyl fluorescein analogs. The study aimed to introduce a facile and environmentally sustainable strategy for efficiently producing alternate potent bioactivity agents.

Background

Population growth trends, limited efficacy and side effects of available medicine, and new challenges like antibiotic resistance have led to the urgent need for more and better pharmaceuticals and a notable increase in drug development. The global health demands and significant medicinal value of thioamidoalkyl compounds prompted synthesizing new fluorescein-based thioamidoalkyl derivatives to explore their prospective biomedical potential.

Methods

To prepare thioamidoalkyl fluorescein analogs, a solvent-free three-component reaction of fluorescein with aryl aldehydes and thiobenzamide catalyzed by boric acid was used. The antibacterial potentials of thioamidoalkyl fluorescein analogs against () bacteria were analyzed in terms of half-maximal inhibitory concentration (IC). Moreover, molecular docking experiments explored the binding affinities and possible interaction mechanisms between newly synthesized analogs and active sites of adhesion protein FimH.

Results

FTIR, 1H, and 13C NMR results verified the successful formation of all analogs. The experimental and theoretical antibacterial activity results confirmed that the compound M-11 is relatively more potent against based on lower IC values of 54.14 nM and binding energy value of ‒6.30 kcal/mol (comparable to ‒6.70 kcal/mol of reference ligand) probably because of unique structure and strong binding affinities for target protein structure.

Conclusion

The findings demonstrated the potential of the currently employed synthetic approach to produce new analogs with decent yields facilely. Interestingly, the M-11 compound proved to be an excellent prospective source of antibiotic drugs based on both experimental and computational analyses.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cocat/10.2174/0122133372319377241218122708
2025-01-21
2025-09-27

  • From This Site

    /content/journals/cocat/10.2174/0122133372319377241218122708
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. CoppolaG.A. PillitteriS. Van der EyckenE.V. YouS.L. SharmaU.K. Multicomponent reactions and photo/electrochemistry join forces: Atom economy meets energy efficiency.Chem. Soc. Rev.20225162313238210.1039/D1CS00510C 35244107
     [Google Scholar]
  2. FaizanS. RoohiT.F. RajuR.M. SivamaniY. BrP.K. A century-old one-pot multicomponent Biginelli reaction products still finds a niche in drug discoveries: Synthesis, mechanistic studies and diverse biological activities of dihydropyrimidines.J. Mol. Struct.2023129113602010.1016/j.molstruc.2023.136020
     [Google Scholar]
  3. GraziaM.M. GiannessiL. RadiM. Multicomponent synthesis of purines and pyrimidines: From the origin of life to new sustainable approaches for drug‐discovery applications.Eur. J. Org. Chem.2023262e20220128810.1002/ejoc.202201288
     [Google Scholar]
  4. RussoC. BrunelliF. Cesare TronG. GiustinianoM. Isocyanide‐based multicomponent reactions promoted by visible light photoredox catalysis.Chemistry20232915e20220315010.1002/chem.202203150 36458647
     [Google Scholar]
  5. dos SantosJ.A. de CastroP.P. de OliveiraK.T. BrocksomT.J. AmaranteG.W. Multicomponent reactions applied to total synthesis of biologically active molecules: A short review.Curr. Top. Med. Chem.20232311990100310.2174/1568026623666230403102437 37016527
     [Google Scholar]
  6. AfzaN. FatmaS. GhousF. ShuklaS. RaiS. SrivastavaK. BishnoiA. An efficient multicomponent synthesis, characterization, SAR, In-silico ADME prediction and molecular docking studies of 2-Amino-7-(substituted-phenyl)-3-cyano-4-phenyl-4,5,6,7-tetrahydropyrano[2,3-b] pyrrole-5-carboxylic acid derivatives and their in-vitro antimicrobial activity.J. Mol. Struct.2023127613472110.1016/j.molstruc.2022.134721
     [Google Scholar]
  7. MessireG. CailletE. Berteina-RaboinS. Green catalysts and/or green solvents for sustainable multi-component reactions.Catalysts202414959310.3390/catal14090593
     [Google Scholar]
  8. PatelS.G. PatelP.J. UpadhyayD.B. PuertaA. MalikA. KandukuriN.K. SharmaR.K. PadrónJ.M. PatelH.M. Insights into microwave assisted synthesis of spiro-chromeno[2,3-d]pyrimidines using PEG-OSO3H catalyst: DFT study and their antiproliferative activity.J. Mol. Struct.2023129213617410.1016/j.molstruc.2023.136174
     [Google Scholar]
  9. GoswamiU.J. XalxoA. KhanA.T. Catalyst‐and solvent‐free synthesis of pentacyclic‐dione derivatives from 4‐hydroxythiocoumarin and aldehyde using pseudo‐three‐component reaction.ChemistrySelect2023835e20230252010.1002/slct.202302520
     [Google Scholar]
  10. ToorbafM. MoradiL. DehghaniA. Preparation of GO/Cys-Cu(II) as a novel, effective and recoverable catalyst for the multi component synthesis of spirooxindoles under mild conditions.J. Mol. Struct.2023129413633510.1016/j.molstruc.2023.136335
     [Google Scholar]
  11. DömlingA. UgiI. Multicomponent reactions with isocyanides.Angew. Chem. Int. Ed.200039183168321010.1002/1521‑3773(20000915)39:18<3168::AID‑ANIE3168>3.0.CO;2‑U 11028061
     [Google Scholar]
  12. Monika; Chander; Ram, S.; Sharma, P.K. A review on molecular iodine catalyzed/mediated multicomponent reactions.Asian J. Org. Chem.2023121e20220061610.1002/ajoc.202200616
     [Google Scholar]
  13. GomesC. CostaM. LopesS.M.M. NogueiraB.A. FaustoR. PaixãoJ.A. Pinho e MeloT.M.V.D. MartinsL.M.D.R.S. PineiroM. On the mechanochemical synthesis of C-scorpionates with an oxime moiety and their application in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction.New J. Chem.202448287488610.1039/D3NJ05017C
     [Google Scholar]
  14. LakhaniP. KaneS. SrivastavaH. GoutamU.K. ModiC.K. Sustainable approach for the synthesis of chiral β-aminoketones using an encapsulated chiral Zn(II)–salen complex.RSC Sustainability2023171773178210.1039/D3SU00210A
     [Google Scholar]
  15. SalamiS.A. SafariJ.B. SmithV.J. KrauseR.W.M. Mechanochemically‐assisted Passerini reactions: A practical and convenient method for the synthesis of novel α‐acyloxycarboxamide derivatives.ChemistryOpen2023125e20220026810.1002/open.202200268 37198143
     [Google Scholar]
  16. KumarS. AroraA. KumarS. KumarR. MaityJ. SinghB.K. Passerini reaction: Synthesis and applications in polymer chemistry.Eur. Polym. J.202319011200410.1016/j.eurpolymj.2023.112004
     [Google Scholar]
  17. WolfsJ. RibcaI. MeierM.A.R. JohanssonM. Polythionourethane thermoset synthesis via activation of elemental sulfur in an efficient multicomponent reaction approach.ACS Sustain. Chem.& Eng.20231193952396210.1021/acssuschemeng.3c00143
     [Google Scholar]
  18. CoresÁ. CleriguéJ. Orocio-RodríguezE. MenéndezJ.C. Multicomponent reactions for the synthesis of active pharmaceutical ingredients.Pharmaceuticals (Basel)2022158100910.3390/ph15081009 36015157
     [Google Scholar]
  19. BuskesM.J. CoffinA. TroastD.M. SteinR. BlancoM.J. Accelerating drug discovery: Synthesis of complex chemotypes via multicomponent reactions.ACS Med. Chem. Lett.202314437638510.1021/acsmedchemlett.3c00012 37077380
     [Google Scholar]
  20. WangF. LangleyR. GultenG. DoverL.G. BesraG.S. JacobsW.R.Jr SacchettiniJ.C. Mechanism of thioamide drug action against tuberculosis and leprosy.J. Exp. Med.20072041737810.1084/jem.20062100 17227913
     [Google Scholar]
  21. DamodiranM. Panneer SelvamN. PerumalP.T. Synthesis of highly functionalized oxazines by Vilsmeier cyclization of amidoalkyl naphthols.Tetrahedron Lett.200950395474547810.1016/j.tetlet.2009.07.051
     [Google Scholar]
  22. MalekiB. SheikhE. SereshtE.R. EshghiH. AshrafiS.S. KhojastehnezhadA. VeisiH. One-pot synthesis of 1-amidoalkyl-2-naphthols catalyzed by polyphosphoric acid supported on silica-coated NiFe2O4 nanoparticles.Org. Prep. Proced. Int.2016481374410.1080/00304948.2016.1127098
     [Google Scholar]
  23. PetkovH. SimeonovS.P. Amidoalkyl naphthols as important bioactive substances and building blocks: A review on the current catalytic Mannich-type synthetic approaches.Appl. Sci. (Basel)20231311661610.3390/app13116616
     [Google Scholar]
  24. KusakabeY. NagatsuJ. ShibuyaM. KawaguchiO. HiroseC. ShiratoS. Minimycin, a new antibiotic.J. Antibiot. (Tokyo)1972251444710.7164/antibiotics.25.44 5010645
     [Google Scholar]
  25. LesherG.Y. SurreyA.R. A new method for the preparation of 3-substituted-2-oxazolidones.J. Am. Chem. Soc.195577363664110.1021/ja01608a032
     [Google Scholar]
  26. RenH. GradyS. GamenaraD. HeinzenH. MoynaP. CroftS.L. KendrickH. YardleyV. MoynaG. Design, synthesis, and biological evaluation of a series of simple and novel potential antimalarial compounds.Bioorg. Med. Chem. Lett.200111141851185410.1016/S0960‑894X(01)00308‑0 11459645
     [Google Scholar]
  27. ClarkR.D. CaroonJ.M. KlugeA.F. RepkeD.B. RoszkowskiA.P. StrosbergA.M. BakerS. BitterS.M. OkadaM.D. Synthesis and antihypertensive activity of 4′-substituted spiro[4H-3,1-benzoxazine-4,4′-piperidin]-2(1H)-ones.J. Med. Chem.198326565766110.1021/jm00359a007 6842505
     [Google Scholar]
  28. BenediniF. BertoliniG. CeredaR. DonàG. GromoG. LeviS. MizrahiJ. SalaA. New antianginal nitro esters with reduced hypotensive activity. Synthesis and pharmacological evaluation of 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones.J. Med. Chem.199538113013610.1021/jm00001a018 7837224
     [Google Scholar]
  29. MatsuokaH. OhiN. MiharaM. SuzukiH. MiyamotoK. MaruyamaN. TsujiK. KatoN. AkimotoT. TakedaY. YanoK. KurokiT. Antirheumatic agents: Novel methotrexate derivatives bearing a benzoxazine or benzothiazine moiety.J. Med. Chem.199740110511110.1021/jm9605288 9016334
     [Google Scholar]
  30. MosherH.S. FrankelM.B. GregoryM. Heterocyclic diphenylmethane derivatives.J. Am. Chem. Soc.195375215326532810.1021/ja01117a054
     [Google Scholar]
  31. RemillardS. RebhunL.I. HowieG.A. KupchanS.M. Antimitotic activity of the potent tumor inhibitor maytansine.Science197518942071002100510.1126/science.1241159 1241159
     [Google Scholar]
  32. KunduT. MitraB. GhoshP. Humic acid: An unexplored organocatalyst toward the synthesis of 1-amidoalkyl-2-naphthols and 1-thioamidoalkyl-2-naphthols through one-pot multi-component system.Synth. Commun.202353191588160010.1080/00397911.2023.2236737
     [Google Scholar]
  33. ShenA. TsaiC. ChenC. Synthesis and cardiovascular evaluation of N-substituted 1-aminomethyl-2-naphthols.Eur. J. Med. Chem.1999341087788210.1016/S0223‑5234(99)00204‑4
     [Google Scholar]
  34. GyémántN. EngiH. SchelzZ. SzatmáriI. TóthD. FülöpF. MolnárJ. de WitteP.A.M. In vitro and in vivo multidrug resistance reversal activity by a Betti-base derivative of tylosin.Br. J. Cancer2010103217818510.1038/sj.bjc.6605716 20551959
     [Google Scholar]
  35. KidwaiM. ChauhanR. Catalyst‐free synthesis of Betti bases in a Mannich‐type reaction.Asian J. Org. Chem.20132539539810.1002/ajoc.201300039
     [Google Scholar]
  36. KhazaeiA. AbbasiF. Moosavi-ZareA.R. KhazaeiM. BeyzaviM.H. Condensation of aryl aldehydes, 2‐naphthol, and thioacetamide catalyzed by n‐halo reagents in neutral media.J. Chin. Chem. Soc. (Taipei)2015621085085410.1002/jccs.201500125
     [Google Scholar]
  37. WeiH.X. LuD. SunV. ZhangJ. GuY. OsenkowskiP. YeW. SelkoeD.J. WolfeM.S. Augelli-SzafranC.E. Part 2. Notch-sparing γ-secretase inhibitors: The study of novel γ-amino naphthyl alcohols.Bioorg. Med. Chem. Lett.20162692133213710.1016/j.bmcl.2016.03.042 27020305
     [Google Scholar]
  38. SaadonK.E. TahaN.M.H. MahmoudN.A. ElhagaliG.A.M. RagabA. Synthesis, characterization, and in vitro antibacterial activity of some new pyridinone and pyrazole derivatives with some in silico ADME and molecular modeling study.J. Indian Chem. Soc.20221993899391710.1007/s13738‑022‑02575‑y
     [Google Scholar]
  39. HassanzadehF. JafariE. MohammadiT. Jahanian-NajafabadiA. Synthesis and antimicrobial evaluation of some 2,5 disubstituted 1,3,4-oxadiazole derivatives.Res. Pharm. Sci.201712433033610.4103/1735‑5362.212051 28855945
     [Google Scholar]
  40. ChawlaP. SinghR. SarafS.K. Effect of chloro and fluoro groups on the antimicrobial activity of 2,5-disubstituted 4-thiazolidinones: A comparative study.Med. Chem. Res.201221103263327110.1007/s00044‑011‑9864‑1
     [Google Scholar]
  41. KrammerE.M. De RuyckJ. RoosG. BouckaertJ. LensinkM.F. Targeting dynamical binding processes in the design of non-antibiotic anti-adhesives by molecular simulation—The example of FimH.Molecules2018237164110.3390/molecules23071641 29976867
     [Google Scholar]
/content/journals/cocat/10.2174/0122133372319377241218122708
Loading
Synthesis and Characterization of Thioamidoalkyl Fluorescein Analogs for Antibacterial Activity and Molecular Docking Analyses
Curr. Organocatal. 12, 167 (2025); https://doi.org/10.2174/0122133372319377241218122708
/content/journals/cocat/10.2174/0122133372319377241218122708
/content/journals/cocat/10.2174/0122133372319377241218122708
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): antibacterial activity; aromatic aldehydes; fluorescein analogs; molecular docking; Multicomponent reactions; one-pot synthesis; thioamidoalkyl

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