Skip to main content
SpringerLink
Log in

Design, synthesis, molecular docking and biological studies of some novel pyrrolidine-triazole-aurone hybrids against digestive enzymes

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

Abstract

Here in this work we successfully designed and synthesized a library of some novel pyrrolidine-triazole-aurone hybrids i.e. (Z)-2-benzylidene-6-((1-(2-(pyrrolidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)benzofuran-3(2H)-one derivatives 5(a-k). The structures of all the synthesized hybrid aurones were confirmed based on their spectral (FT-IR, 1H NMR, 13C NMR) and HRMS data. In biological studies, the impact of synthesized compounds on digestive enzymes, amylase, lipase, and trypsin was analyzed. These compounds exhibited varying effects on these enzymes as both trypsin and amylase were activated, but a significant inhibition was achieved for the lipase enzyme. Upon examining the binding energies of the synthesized compounds with the enzymes, it was observed that the experimental findings partially aligned with the docking results. These in vitro and in silico results of these hybrid aurones against digestive enzymes, signify their potential as anti-inflammatory and anti-obesity agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Scheme 1
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

Data supporting the findings of this manuscript (spectral and biological data) is either included in the manuscript or provided as supplementary data.

References

  1. F. Liu, D. Lv, L. Wang, X. Feng, R. Zhang, W. Liu, W. Han, BMC Pediatr. 22, 1 (2022)

    Article  CAS  Google Scholar 

  2. J.A. Bell, M. Kivimaki, M. Hamer, Obes. Rev. 15, 504 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. A. Abdullah, A. Peeters, M. de Courten, J. Stoelwinder, Diabetes Res. Clin. Pract. 89, 309 (2010)

    Article  PubMed  Google Scholar 

  4. P.W. Wilson, R.B. D’Agostino, L. Sullivan, H. Parise, W.B. Kannel, Arch. Intern. Med. 162, 1867 (2002)

    Article  PubMed  Google Scholar 

  5. Y. Lu, K. Hajifathalian, M. Ezzati, M. Woodward, E.B. Rimm, G. Danaei, C. D’Este, Lancet 383, 970 (2014)

    Article  PubMed  Google Scholar 

  6. E.E. Calle, M.J. Thun, Oncogene 23, 6365 (2004)

    Article  CAS  PubMed  Google Scholar 

  7. H.L. Daneschvar, M.D. Aronson, G.W. Smetana, Am. J. Med. 129, 879 (2016)

    Article  Google Scholar 

  8. K. Woodard, L. Louque, D.S. Hsia, Ther. Adv. Endocrinol. Metab. 11, 2042018820918789 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  9. E. Pilitsi, O.M. Farr, S.A. Polyzos, N. Perakakis, E. Nolen-Doerr, A.-E. Papathanasiou, C.S. Mantzoros, Metabolism 92, 170 (2019)

    Article  CAS  PubMed  Google Scholar 

  10. T.-T. Liu, X.-T. Liu, Q.-X. Chen, Y. Shi, Biomed. Pharmacother. 128, 110314 (2020)

    Article  CAS  PubMed  Google Scholar 

  11. N.M. Aldossari, E.E. El Gabry, G.E. Gawish, Medicine 98, e15878 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. D. Shah, K. Mital, Adv. Ther. 35, 31 (2018)

    Article  CAS  PubMed  Google Scholar 

  13. B. Seligman, Angiology 6, 208 (1955)

    Article  CAS  PubMed  Google Scholar 

  14. T.N. Shamsi, R. Parveen, S. Afreen, M. Azam, P. Sen, Y. Sharma, Q.M.R. Haque, T. Fatma, N. Manzoor, S. Fatima, J. Diet. Suppl. 15, 939 (2018)

    Article  CAS  PubMed  Google Scholar 

  15. J. Jampilek, Molecules 24, 3839 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. B. Saroha, G. Kumar, M. Kumari, R. Kaur, N. Raghav, P.K. Sharma, N. Kumar, S. Kumar, Int. J. Biol. Macromol. 222, 2270 (2022)

    Article  CAS  PubMed  Google Scholar 

  17. W. Yu, Z.-W. Zhai, D.E. Wedge, S.O. Duke, H.-K. Wu, J.-Q. Weng, C.-X. Tan, Y.-G. Zhang, X.-H. Liu, Res. Chem. Intermed. 45, 5989 (2019)

    Article  CAS  Google Scholar 

  18. S. Narwal, S. Kumar, P.K. Verma, Res. Chem. Intermed. 47, 1625 (2021)

    Article  CAS  Google Scholar 

  19. A. Gomtsyan, Chem. Heterocycl. Compd. 48, 7 (2012)

    Article  CAS  Google Scholar 

  20. P. Pinto, C.M. Machado, J. Moreira, J.D.P. Almeida, P.M. Silva, A.C. Henriques, J.X. Soares, J.A. Salvador, C. Afonso, M. Pinto, Eur. J. Med. Chem. 184, 111752 (2019)

    Article  CAS  PubMed  Google Scholar 

  21. K. Wen, X. Fang, J. Yang, Y. Yao, K.S. Nandakumar, M.L. Salem, K. Cheng, Curr. Med. Chem. 28, 1042 (2021)

    Article  CAS  PubMed  Google Scholar 

  22. N.J. Lawrence, D. Rennison, A.T. McGown, J.A. Hadfield, Bioorg. Med. Chem. Lett. 13, 3759 (2003)

    Article  CAS  PubMed  Google Scholar 

  23. J. Wang, N. Wang, X. Yao, S. Kitanaka, Asian J. Tradit. Med. 2, 23 (2007)

    CAS  Google Scholar 

  24. M. Roussaki, S. Costa Lima, A.-M. Kypreou, P. Kefalas, A.C. da Silva, A. Detsi, Int. J. Med. Chem. 2012, 1 (2012)

    Google Scholar 

  25. B.P. Bandgar, S.A. Patil, B.L. Korbad, S.C. Biradar, S.N. Nile, C.N. Khobragade, Eur. J. Med. Chem. 45, 3223 (2010)

    Article  CAS  PubMed  Google Scholar 

  26. H.H. Jardosh, M.P. Patel, Arab. J. Chem. 10, S3781 (2017)

    Article  CAS  Google Scholar 

  27. M. Zhang, X.H. Xu, Y. Cui, L.G. Xie, C.H. Kong, Pest Manag. Sci. 68, 1512 (2012)

    Article  CAS  PubMed  Google Scholar 

  28. R. Haudecoeur, A. Ahmed-Belkacem, W. Yi, A. Fortuné, R. Brillet, C. Belle, E. Nicolle, C. Pallier, J.M. Pawlotsky, A. Boumendjel, J. Med. Chem. 54, 5395 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. R. Sheng, Y. Xu, C. Hu, J. Zhang, X. Lin, J. Li, B. Yang, Q. He, Y. Hu, Eur. J. Med. Chem. 44, 7 (2009)

    Article  CAS  PubMed  Google Scholar 

  30. M.P. Carrasco, A.S. Newton, L. Gonçalves, A. Góis, M. Machado, J. Gut, F. Nogueira, T. Hänscheid, R.C. Guedes, D.J.V.A. dos Santos, P.J. Rosenthal, R. Moreira, Eur. J. Med. Chem. 80, 523 (2014)

    Article  CAS  PubMed  Google Scholar 

  31. F. Souard, S. Okombi, C. Beney, S. Chevalley, A. Valentin, A. Boumendjel, Bioorg. Med. Chem. 18, 5724 (2010)

    Article  CAS  PubMed  Google Scholar 

  32. M. Protopopov, V. Vdovin, S. Starosyla, I. Borysenko, A. Prykhod’ko, S. Lukashov, Y. Bilokin, V. Bdzhola, S. Yarmoluk, Bioorg. Chem. 102, 104062 (2020)

    Article  CAS  PubMed  Google Scholar 

  33. M. Morimoto, H. Fukumoto, T. Nozoe, A. Hagiwara, K. Komai, J. Agric. Food Chem. 55, 700 (2007)

    Article  CAS  PubMed  Google Scholar 

  34. B. Saroha, G. Kumar, R. Kumar, M. Kumari, S. Kumar, Chem. Biol. Drug Des. 100, 843 (2022)

    Article  CAS  PubMed  Google Scholar 

  35. J. Mi, J. Wu, C. Zhou, J. Pharmacol. Sci. 23, 84 (2008)

    CAS  Google Scholar 

  36. M. Akter, K. Rupa, P. Anbarasan, Chem. Rev. 122, 13108 (2022)

    Article  CAS  PubMed  Google Scholar 

  37. M. Marinescu, Antibiotics 12, 1220 (2023)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. W. Ouellette, S. Jones, J. Zubieta, CrystEngComm 13, 4457 (2011)

    Article  CAS  Google Scholar 

  39. C.H. Zhou, Y. Wang, Curr. Med. Chem. 19, 239 (2012)

    Article  CAS  PubMed  Google Scholar 

  40. R. Jalaja, S.G. Leela, P.K. Valmiki, C.T.F. Salfeena, K.T. Ashitha, V.R.D. Krishna Rao, M.S. Nair, R.K. Gopalan, S.B. Somappa, ACS Med. Chem. Lett. 9, 662 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. D.R. Buckle, C.J. Rockell, H. Smith, B.A. Spicer, J. Med. Chem. 29, 2262 (1986)

    Article  CAS  PubMed  Google Scholar 

  42. M. Asif, Chem. Int. 1, 174 (2015)

    CAS  Google Scholar 

  43. S.H. Sumrra, W. Zafar, M. Imran, Z.H. Chohan, J. Coord. Chem. 75, 293 (2022)

    Article  CAS  Google Scholar 

  44. G.C. Tron, T. Pirali, R.A. Billington, P.L. Canonico, G. Sorba, A.A. Genazzani, Med. Res. Rev. 28, 278 (2008)

    Article  CAS  PubMed  Google Scholar 

  45. G. Kumar, B. Saroha, R. Kumar, M. Kumari, S. Dalal, S. Kumar, J. Heterocycl. Chem. 59, 297 (2022)

    Article  CAS  Google Scholar 

  46. B. Saroha, G. Kumar, S. Kumar, M. Kumari, M. Rani, N. Raghav, P.K. Sahoo, S. Ghosh, S. Mahata, V.D. Nasare, Eur. J. Med. Chem. Rep. 5, 100056 (2022)

    CAS  Google Scholar 

  47. B. Saroha, G. Kumar, S. Kumar, M. Kumari, M. Rani, N. Raghav, P.K. Sahoo, S. Ghosh, S. Mahata, V.D. Nasare, Curr. Res. Green Sustain. Chem. 5, 100295 (2022)

    Article  CAS  Google Scholar 

  48. B. Saroha, G. Kumar, P. Arya, N. Raghav, S. Kumar, Bioorg. Chem. 140, 106805 (2023)

    Article  CAS  PubMed  Google Scholar 

  49. G. Kumar, E. Lathwal, B. Saroha, S. Kumar, S. Kumar, N.S. Chauhan, T. Kumar, ChemistrySelect 5, 3539 (2020)

    Article  CAS  Google Scholar 

  50. S. Kumar, Green Chem. Lett. Rev. 7, 95 (2014)

    Article  ADS  Google Scholar 

  51. F. Antoni, D. Wifling, G. Bernhardt, Eur. J. Med. Chem. 210, 112958 (2021)

    Article  CAS  PubMed  Google Scholar 

  52. E. Kashani-Amin, P. Yaghmaei, B. Larijani, A. Ebrahim-Habibi, Obes. Res. Clin. Pract. 7, e487 (2013)

    Article  PubMed  Google Scholar 

  53. P. Arya, N. Raghav, J. Mol. Struct. 1228, 129774 (2021)

    Article  CAS  Google Scholar 

  54. B. Saroha, G. Kumar, E. Lathwal, S. Kumar, M. Kumari, N. Mor, N. Raghav, S. Kumar, Chem. Data Collect. 31, 100630 (2021)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Authors are thankful to Kurukshetra University Kurukshetra for lab facility and other support, DST-New Delhi for NMR support through FIST Programme 2017 (SR/FST/CS-1).

Funding

Author Suresh Kumar acknowledges Kurukshetra University Kurukshetra for the financial assistance in the form of seed money grant (DPA-I/32/22/MRP/2358-2500).

Author information

Authors and Affiliations

  1. Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India

    Sanjeev Kumar, Ekta Lathwal, Bhavna Saroha, Gourav Kumar, Arpana Bhardwaj, Poonam Bishnoi, Manishita Rani, Neera Raghav, Ramesh Kumar & Suresh Kumar

  2. Department of Chemistry, Govt. College, Tigaon, Faridabad, Haryana, 121101, India

    Ekta Lathwal

  3. Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, 97201, USA

    Gourav Kumar

Authors
  1. Sanjeev Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ekta Lathwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bhavna Saroha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gourav Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arpana Bhardwaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Poonam Bishnoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manishita Rani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Neera Raghav
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ramesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Suresh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SK & BS—designed the research work; SK, AB & PB—performed the research work; GK—analysed the spectral data and performed molecular docking studies; MR—did biological screening; BS—did computational study (ADME) and analysed the results; SK & EL—wrote the manuscript; NR—supervision of biological studies; RK—proofread the manuscript; SK*—overall supervision of the project. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Suresh Kumar.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest in publishing this article.

Ethical approval

No animal/human studies were carried out in the present work.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 2693 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, S., Lathwal, E., Saroha, B. et al. Design, synthesis, molecular docking and biological studies of some novel pyrrolidine-triazole-aurone hybrids against digestive enzymes. Res Chem Intermed 50, 1249–1271 (2024). https://doi.org/10.1007/s11164-023-05221-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-023-05221-1

Keywords

Search

Navigation