SpringerLink
Log in

Design, synthesis, characterization, and docking studies of hiherto unkown chlorinated thiazolidine, thiophene, and 2-iminochromene derivatives as protein-like protease inhibitors

  • Original Paper
  • Published:
Journal of the Iranian Chemical Society Aims and scope Submit manuscript

Abstract

The present work details the synthesis of several intriguing nitrogenous heterocycles utilizing a cyano-N-aryl-acetamide-reagent, notably chlorinated thiazolidine, thiophene and 2-iminochromene derivatives. Thus, the precursor 2-cyano-N-(2,4-dichlorophenyl) acetamide 1 underwent the reaction with phenyl isothiocyanate in DMF/KOH to afford the intermediate salt 3, which reacted in situ with several α-halogenated reagents 4a-c like ethylchloroacetate,α-bromoethylpropionate and α-bromo ethyl butaneoate and afforded the corresponding 4-thiazolidinnone derivatives (6a–c, yield%; 67–85), thiophene derivatives (11;yield 80%) and (15, yield 77%) obtained from the reaction of 3 with α- chloroacetyl acetone 9 and ethyl 2-chloro-3-oxobutanoate 12.Novel series of different 4-thiazolidinones(16a–e; yield%; 65–84) were obtained via condensation of 6a with different aldehydes. Finally, the reaction of compound 1 with different bifunctional reagents, such as salicylaldehyde derivatives and 2-hydroxynaphthaldehyde, in ethanol furnished the iminochromenes (17a,b; yield %77,80) and (18; yield 85%). In addition, molecular docking studies of the prepared molecules were carried out against papain-like protease (PLpro) to identify novel promising inhibitors of Coronavirus Disease COVID-19. The binding affinity of the best docked compounds 16c and 16a toward the target enzyme was − 9.6 and − 8.9 kcal/mole, respectively. In silico-docking-Studies indicate, that compounds 16c and 16a have the potential as antiviral against COVID-19.

Graphical abstract

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Fig. 1
Fig. 2

References

  1. K.M. El-Gaml, Am. J. Org. Chem. 5, 1–9 (2015)

    Google Scholar 

  2. E.S. Darwish, A.M.A. Fattah, F.A. Attaby, O.N. Al-Shayea, Int. J. Mol. Sci. 15, 1237–1254 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  3. A.D. Panchal, P.D. Kunjadia, P.M. Patel, Int. J. Pharm. Sci. Drug Res. 3, 331–337 (2011)

    CAS  Google Scholar 

  4. A.M. Alafeefy, S. Isik, H.A. Abdel-Aziz, A.E. Ashour, D. Vullo, N.A. Al-Jaber, C.T. Supuran, Bioorg. Med. Chem. 21, 1396–1403 (2013)

    Article  CAS  PubMed  Google Scholar 

  5. M. Arora, J. Saravanan, S. Mohan, S. Bhattacharjee, Int. J. Pharm. Pharm. Sci. 5, 315–319 (2013)

    CAS  Google Scholar 

  6. K. Khokhani, T. Khatri, P. Patel, J. Korean Chem. Soc. 57, 476–482 (2013)

    Article  CAS  Google Scholar 

  7. A.A. Fadda, M.M. Mukhtar, H.M. Refat, Am. J. Org. Chem. 2, 32–40 (2012)

    Article  Google Scholar 

  8. M.S. Al-Saadi, H.M. Faidallah, S.A.F. Rostom, Arch. Pharm. 341, 424–434 (2008)

    Article  CAS  Google Scholar 

  9. S. Bondock, R. Rabie, H.A. Etman, A.A. Fadda, Eur. J. Med. Chem. 43, 2122–2129 (2008)

    Article  CAS  PubMed  Google Scholar 

  10. S. Bondock, W. Khalifa, A.A. Fadda, Eur. J. Med. Chem. 42, 948–954 (2007)

    Article  CAS  PubMed  Google Scholar 

  11. P. Karegoudar, M.S. Karthikeyan, D.J. Prasad, M. Mahalinga, B.S. Holla, N.S. Kumari, Eur. J. Med. Chem. 43, 261–267 (2008)

    Article  CAS  PubMed  Google Scholar 

  12. J.Z. Chandanshive, B.G. Pedro, W. Tiznado, B.F. Bonini, J. Caballero, C. Femoni, Tetrahedron 68, 3319–3328 (2012)

    Article  CAS  Google Scholar 

  13. A.A. Bekhit, T.A. Aziem, Bioorg. Med. Chem. 12, 1935–1945 (2004)

    Article  CAS  PubMed  Google Scholar 

  14. T. El-Emary, S. El-Mohsen, Molecules 17, 14464–14483 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. A.A. Abu-Hashem, M.A. Gouda, F.A. Badria, Eur. J. Med. Chem. 45, 1976–1981 (2010)

    Article  CAS  PubMed  Google Scholar 

  16. M.A. Gouda, M.A. Berghot, G.E. Abd El-Ghani, A.M. Khalil, Eur. J. Med. Chem. 45, 1338–1345 (2010)

    Article  CAS  PubMed  Google Scholar 

  17. A.M. Khalil, M.A. Berghot, M.A. Gouda, Eur. J. Med. Chem. 44, 4434–4440 (2009)

    Article  CAS  PubMed  Google Scholar 

  18. M.A. Gouda, M.A. Berghot, A.I. Shoeib, A.M. Khalil, Phosph., Sulfur, Sil. Relat. Elements 185, 1455–1462 (2010)

    Article  CAS  Google Scholar 

  19. M.A. Gouda, A.A. Abu-Hashem, Arch. Pharm. 11, 170–177 (2011)

    Article  Google Scholar 

  20. M.J. Wilby, P.J. Hutchinson, CNS Drug Rev. 10, 281–294 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. J.J. Harnett, V. Roubert, C. Dolo, C. Charnet, B. Spinnewyn, S. Cornet, A. Rolland, J.G. Marin, D. Bigg, P.E. Chabrier, Bioorg. Med. Chem. Lett. 14, 157–160 (2004)

    Article  CAS  PubMed  Google Scholar 

  22. R. Lesyk, B. Zimenkovsky, D. Atamanyuk, F. Jensen, K.K. Kononowicz, A. Gzella, Bioorg. Med. Chem. 14, 5230–5240 (2006)

    Article  CAS  PubMed  Google Scholar 

  23. K. Kashfi, Adv. Pharmacol. 57, 31–89 (2009)

    Article  CAS  PubMed  Google Scholar 

  24. P.R. Modiya, C.N. Patel, Org. Med. Chem. Lett. 2, 29 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  25. M.S. Al-Said, M.M. Ghorab, Y.M. Nissan, Chem. Cent. J. 6, 64 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. P.S. Dragovich, T.J. Prins, R. Zhou, E.L. Brown, F.C. Maldonado, S.A. Fuhrman, L.S. Zalman, T. Tuntl, C.A. Lee, A.K. Patick, J. Med. Chem. 45, 1607–1623 (2002)

    Article  CAS  PubMed  Google Scholar 

  27. P.S. Dragovich, T.J. Prins, R. Zhou, T.O. Johnson, E.L. Brown, F.C. Maldonado, S.A. Fuhrman, L.S. Zalman, A.K. Patick, D.A. Matthews, Bioorg. Med. Chem. Lett. 12, 733–738 (2002)

    Article  CAS  PubMed  Google Scholar 

  28. D. Ye, Y. Zhang, F. Wang, M. Zheng, X. Zhang, X. Luo, X. Shen, H. Jiang, H. Liu, Bioorg. Med. Chem. 18, 1773–1782 (2010)

    Article  CAS  PubMed  Google Scholar 

  29. R. Kulandasamy, A.V. Adhikari, J.P. Stables, Eur. J. Med. Chem. 44, 4376–4384 (2009)

    Article  CAS  PubMed  Google Scholar 

  30. A.M. Khalil, M.A. Berghot, E.A. Ghada, M.A. Gouda, Eur. J. Med. Chem. 40, 1658–1669 (2010)

    CAS  Google Scholar 

  31. P.M. Ronad, M.N. Noolvi, S. Sapkal, S. Dharbhamulla, V.S. Maddi, Eur. J. Med. Chem. 45, 85–89 (2010)

    Article  CAS  PubMed  Google Scholar 

  32. F. Borges, F. Roleir, L. Santana, E. Uriare, Curr. Med. Chem. 12, 887–916 (2005)

    Article  CAS  PubMed  Google Scholar 

  33. A.A. Fadda, M.A. Berghot, F.A. Amer, D.S. Badway, N.M. Bayoumy, Arch. Pharm. 435, 378–385 (2012)

    Article  Google Scholar 

  34. A.A. Fadda, E.H.E. Youssif, Synth. Commun. 41, 677–694 (2011)

    Article  CAS  Google Scholar 

  35. A. El-Shafei, A.A. Fadda, I.I. Abdel-Gawad, E.H.E. Youssif, Synth. Commun. 39, 2954–2972 (2009)

    Article  CAS  Google Scholar 

  36. K.L. Lahtchev, D.I. Batovska, St.. P. Parushev, V.M. Ubiyvovk, A.A. Sibirny, Eur. J. Med. Chem. 43, 2220–2228 (2008)

    Article  CAS  PubMed  Google Scholar 

  37. I.S. Abdel Hafiz, M.A.M. Abdel Reheim, H.M. Reffat, A.A.M. Sarhan, Heterocycles 102(2), 291–317 (2021)

    Article  CAS  Google Scholar 

  38. M.A.M. Abdel Reheim, I.S. Abdel Hafiz, H.S.E. Abdel Rady, Mol. Diver. 26, 741–755 (2022)

    Article  CAS  Google Scholar 

  39. M.A. Mostafa, A.M. Ashmawy, M.A.M. Abdel Reheim, M.A. Bedair, A.M. Abuelela, J. Mol. Struct. 1236, 130292–130294 (2021)

    Article  CAS  Google Scholar 

  40. G.A.M. El-Hag Ali, M.H. Helal, Y.A. Mohamed, A.A. Ali, Y.A. Ammar, J. Chem. Res. 34(8), 459–464 (2010)

    Article  CAS  Google Scholar 

  41. A.M. Fahim, A.M. Farag, M.R. Shaaban, E.A. Ragab, Eur. J. Chem. 9(1), 30–38 (2018)

    Article  CAS  Google Scholar 

  42. A.S. Radwana, M.A.A. Khalida, J. Heterocycl. Chem. 56, 1063–1074 (2019)

    Article  Google Scholar 

  43. A.A. Fadda, N.M. Bayoumy, N.N. Soliman, D.M. Eldiastya, J. Heterocycl. Chem. 56, 597–607 (2019)

    Article  CAS  Google Scholar 

  44. E. Abdel-Latifa, T.K. Khataba, A. Fekria, M.E. Khalifa, Russ. J. Gen. Chem. 91, 1767–1773 (2021)

    Article  Google Scholar 

  45. F. Keshavarzipour, H. Tavakol, Appl. Organomet. Chem. 31(8), 1–8 (2017)

    Article  Google Scholar 

  46. D. Farabi, H. Tavakol, J. Iran. Chem. Soc. 13, 2143–2153 (2016)

    Article  Google Scholar 

  47. D. Shahabi, H. Tavakol, J. Iran. Chem. Soc. 14, 135–142 (2017)

    Article  CAS  Google Scholar 

  48. B. Abtahi, H. Tavakol, Appl. Organomet. Chem. 35(12), 1–8 (2021)

    Article  Google Scholar 

  49. Y.A. Ammar, M.M. Ali, Y.A. Mohammed, H.K. Thabet, M.S.A. El-Gaby, Heterocycl. Commun. 19(3), 195–200 (2013)

    Article  CAS  Google Scholar 

Download references

Funding

The article was funded by Alazhar University.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Arish University, Arish, 45511, Egypt

    Mohamed A. M. Abdel Reheim

  2. Department of Chemistry, Faculty of Science (Girls), Al-Azhar University, Nasr City, 11754, Cairo, Egypt

    Khadija E. Saadon, Nadia M. H. Taha & N. A. Mahmoud

  3. Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, 11884, Cairo, Egypt

    Gameel A. M. Elhagali & Mohamed. S. A. El-Gaby

Authors
  1. Mohamed A. M. Abdel Reheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gameel A. M. Elhagali
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Khadija E. Saadon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nadia M. H. Taha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. A. Mahmoud
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mohamed. S. A. El-Gaby
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gameel A. M. Elhagali.

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

Reheim, M.A.M.A., Elhagali, G.A.M., Saadon, K.E. et al. Design, synthesis, characterization, and docking studies of hiherto unkown chlorinated thiazolidine, thiophene, and 2-iminochromene derivatives as protein-like protease inhibitors. J IRAN CHEM SOC (2024). https://doi.org/10.1007/s13738-024-03056-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13738-024-03056-0

Keywords

Search

Navigation