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Novel polyhydroquinoline Schiff’s base derivatives: synthesis, characterization, in vitro α-glucosidase inhibitory, and molecular docking studies

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Abstract

Novel Schiff’s base hydrazone derivatives (1–24) based on polyhydroquinoline (PHQ) were synthesized in good to excellent yields via three step reactions. Compound 1 (starting material) was synthesized through one pot multi-component unsymmetrical Hantzsch reaction by refluxing a mixture of ethyl-2-(2-formylphenoxy)acetate, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent for 6–8 h. The obtained PHQ was then refluxed with hydrazine hydrate in the presence of absolute ethanol for 4–5 h. to get compound 2. Finally, the hydrazide was treated with various substituted aromatic/aliphatic aldehydes to afford the desired hydrazone Schiff’s bases (3–24). All the produced analogues were structurally deduced with the help of LC-HRESI-MS, 1H- and 13C-NMR spectroscopy. The obtained compounds were evaluated for their α-glucosidase activity, where twelve compounds (10, 14, 7, 9, 8, 17, 12, 19, 13, 15, 21, and 11) were found the most active at IC50 ranging between 5.26 and 25.17 µM, compared to acarbose, a standard α-glucosidase inhibitor with IC50 of 873.34 ± 1.67 µM. The best hit compounds were docked within the acarbose binding pocket of α-glucosidase and vetted for their binding affinities.

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The data that support the findings of this study are available from the corresponding author, upon reasonable request.

References

  1. A. Alam, M. Ali, N.U. Rehman, S. Ullah, S.A. Halim, A. Latif, A. Khan, O. Ullah, S. Ahmad, A. Al-Harrasi, Pharmaceuticals 15, 672 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. X.-T. Xu, X.-Y. Deng, J. Chen, Q.-M. Liang, K. Zhang, D.-L. Li, P.-P. Wu, X. Zheng, R.-P. Zhou, Z.-Y. Jiang, Eur. J. Med. Chem. 189, 112013 (2020)

    Article  PubMed  Google Scholar 

  3. A. Alam, M. Ali, A. Latif, N.U. Rehman, S. Saher, A. Khan, S. Ullah, O. Ullah, S.A. Halim, F. Sani, Bioorg. Chem. 128, 106058 (2022)

    Article  CAS  PubMed  Google Scholar 

  4. C.M. Santos, M. Freitas, E. Fernandes, Eur. J. Med. Chem. 157, 1460 (2018)

    Article  CAS  PubMed  Google Scholar 

  5. M. Dhameja, P. Gupta, Eur. J. Med. Chem. 176, 343 (2019)

    Article  CAS  PubMed  Google Scholar 

  6. P. Bytzer, N.J. Talley, J. Hammer, L.J. Young, M.P. Jones, M. Horowitz, Am. J. Gastroenterol. 97, 604 (2002)

    Article  PubMed  Google Scholar 

  7. M.S. Hedrington, S.N. Davis, Expert Opin. Pharmacother. 20, 2229 (2019)

    Article  PubMed  Google Scholar 

  8. S.V. Moelands, P.L. Lucassen, R.P. Akkermans, W.J. De Grauw, F.A. Van de Laar, Cochrane Database Syst. Rev. 12, CD005061 (2018)

    PubMed  Google Scholar 

  9. N.U. Rehman, R. Maqsood, S. Ullah, S.A. Halim, M.U. Anwar, A. Khan, A. Hussain, J. Hussain, A. Al-Harrasi, S. Afr. J. Bot. 148, 88 (2022)

    Article  CAS  Google Scholar 

  10. K. Rafiq, M. Khan, N. Muhammed, A. Khan, N. Ur Rehman, B.E.M. Al-Yahyaei, M. Khiat, S.A. Halim, Z. Shah, R. Csuk, Med. Chem. Res. 30, 712 (2021)

    Article  CAS  Google Scholar 

  11. A. Al-Mulla, Der Pharma Chem. 9, 141 (2017)

    CAS  Google Scholar 

  12. G.M. Ziarani, N.H. Nasab, N. Lashgari, RSC Adv. 6, 38827 (2016)

    Article  Google Scholar 

  13. A. Weyesa, E. Mulugeta, RSC Adv. 10, 20784 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. X.F. Shang, S.L. Morris-Natschke, Y.Q. Liu, X. Guo, X.S. Xu, M. Goto, J.C. Li, G.Z. Yang, K.H. Lee, Med. Res. Rev. 38, 775 (2018)

    Article  CAS  PubMed  Google Scholar 

  15. P. Teng, C. Li, Z. Peng, V.A. Marie, A. Nimmagadda, M. Su, Y. Li, X. Sun, J. Cai, Bioorg. Med. Chem. 26, 3573 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. K. Nakamoto, I. Tsukada, K. Tanaka, M. Matsukura, T. Haneda, S. Inoue, N. Murai, S. Abe, N. Ueda, M. Miyazaki, Bioorg. Med. Chem. Lett. 20, 4624 (2010)

    Article  CAS  PubMed  Google Scholar 

  17. I.A.M. Radini, T.M. Elsheikh, E.M. El-Telbani, R.E. Khidre, Molecules 21, 909 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  18. S. Mukherjee, M. Pal, Drug Discov. Today 18, 389 (2013)

    Article  CAS  PubMed  Google Scholar 

  19. M. Kidwai, N. Negi, Mon. Chem. Chem. Mon. 128, 85 (1997)

    Article  CAS  Google Scholar 

  20. P. Balaji, D. Ranganayakulu, G.S. Reddy, Asian J. Pharm. Pharmacol. 3, 9 (2017)

    CAS  Google Scholar 

  21. N. Muruganantham, R. Sivakumar, N. Anbalagan, V. Gunasekaran, J.T. Leonard, Biol. Pharm. Bull. 27, 1683 (2004)

    Article  CAS  PubMed  Google Scholar 

  22. S.M. Baghbanian, S. Khaksar, S.M. Vahdat, M. Farhang, M. Tajbakhsh, Chin. Chem. Lett. 21, 563 (2010)

    Article  CAS  Google Scholar 

  23. R.C. Brinkerhoff, E. Santa-Helena, P.C. do Amaral, D.C. Cabrera, R.F. Ongaratto, P.M. de Oliveira, C.D.R.M. D’Oca, C.A.N. Gonçalves, L.E.M. Nery, M.G.M. D’Oca, RSC Adv. 9, 24688 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. K. Aswin, K. Logaiya, P.N. Sudhan, S.S. Mansoor, J. Taibah Univ. Sci. 6, 1 (2012)

    Article  Google Scholar 

  25. S. Jadhvar, H. Kasraliker, S. Goswami, A. Chakrawar, S. Bhusare, Res. Chem. Intermed. 43, 7211 (2017)

    Article  CAS  Google Scholar 

  26. R.R. Raslan, S.A. Hessein, S.A. Fouad, N.A. Shmiess, J. Heterocycl. Chem. 59, 832 (2022)

    Article  CAS  Google Scholar 

  27. D.K. Jamale, S.S. Undare, N.J. Valekar, A.P. Sarkate, G.B. Kolekar, P.V. Anbhule, J. Heterocycl. Chem. 56, 608 (2019)

    CAS  Google Scholar 

  28. K. Ahmed, B. Dubey, S. Nadeem, B. Shrivastava, P. Sharma and C. Karthikeyan

  29. A. Kumar, S. Sharma, V.D. Tripathi, R.A. Maurya, S.P. Srivastava, G. Bhatia, A. Tamrakar, A.K. Srivastava, Bioorg. Med. Chem. 18, 4138 (2010)

    Article  CAS  PubMed  Google Scholar 

  30. H. Yu, N.U. Rehman, M. Ali, A. Alam, A. Latif, N. Shahab, I. Amir Khan, A. Jabbar Shah, M. Khan, A. Al-Ghafri, Antibiotics 11, 1568 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  31. S. Mirani Nezhad, E. Nazarzadeh Zare, A. Davarpanah, S.A. Pourmousavi, M. Ashrafizadeh, A.P. Kumar, Molecules 27, 1748 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. G.H.A. Machado, M.V.C. Trento, J.J. Pinelli, R.H. Piccoli, S.S. Thomasi, S. Marcussi (2021)

  33. N.H. Sapariya, B.K. Vaghasiya, R.P. Thummar, R.D. Kamani, K.H. Patel, P. Thakor, S.S. Thakkar, A. Ray, D.K. Raval, New J. Chem. 41, 10686 (2017)

    Article  CAS  Google Scholar 

  34. J.D. Bhatt, T.S. Patel, C.J. Chudasama, K.D. Patel, Chem. Sel. 3, 3632 (2018)

    CAS  Google Scholar 

  35. M. Taha, N.H. Ismail, S. Imran, A. Wadood, F. Rahim, M. Ali, A.U. Rehman, MedChemComm 6, 1826 (2015)

    Article  CAS  Google Scholar 

  36. M. Sepahvand, F. Buazar, M.H. Sayahi, Appl. Organomet. Chem. 34, e6000 (2020)

    Article  CAS  Google Scholar 

  37. X. Zhang, G. Li, D. Wu, Y. Yu, N. Hu, H. Wang, X. Li, Y. Wu, Food Funct. 11, 66 (2020)

    Article  CAS  PubMed  Google Scholar 

  38. N. Ur Rehman, K. Rafiq, A. Khan, S. Ahsan Halim, L. Ali, N. Al-Saady, A. Hilal Al-Balushi, H.K. Al-Busaidi, A. Al-Harrasi, Mar. Drugs 17, 666 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  39. S.A. Halim, S. Jabeen, A. Khan, A. Al-Harrasi, Pharmaceuticals 14, 482 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. I. Khan, A. Khan, S.A. Halim, M. Khan, S. Zaib, B.E.M. Al-Yahyaei, A. Al-Harrasi, A. Ibrar, Int. J. Biol. Macromol. 167, 233 (2021)

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work is supported by the Higher Education Research Endowment Fund for financial support, under research project (HED-041).

Author information

Authors and Affiliations

  1. State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, 100029, China

    Nazish Shahab & Duanyang Kong

  2. Department of Chemistry, University of Malakand, P.O. Box 18800, Dir Lower, Khyber Pakhtunkhwa, Pakistan

    Nazish Shahab, Mumtaz Ali, Aftab Alam, Zainab Zainab, Abdul Latif & Manzoor Ahmad

  3. Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Birkat Al Mauz, Nizwa, Sultanate of Oman

    Najeeb Ur Rehman, Saeed Ullah, Ajmal Khan & Ahmed Al-Harrasi

  4. College of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang, 050024, China

    Zainab Zainab

  5. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Saeed Ullah

  6. Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea

    Masaud Shah

  7. Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Hayatabad Peshawar, Khyber Pakhtunkhwa, Pakistan

    Momin Khan

Authors
  1. Nazish Shahab
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  2. Duanyang Kong
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  3. Mumtaz Ali
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  11. Ajmal Khan
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  12. Ahmed Al-Harrasi
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Contributions

MA and DK: Supervision; MA and MA: Conceptualization; NS, ZZ and AA: Experimental; NUR and AA-H: Spectroscopic analysis; MK, SU and AK: Biological activities; AL and MS: Molecular docking.

Corresponding authors

Correspondence to Duanyang Kong, Ahmed Al-Harrasi or Manzoor Ahmad.

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Shahab, N., Kong, D., Ali, M. et al. Novel polyhydroquinoline Schiff’s base derivatives: synthesis, characterization, in vitro α-glucosidase inhibitory, and molecular docking studies. Res Chem Intermed 49, 3005–3028 (2023). https://doi.org/10.1007/s11164-023-05038-y

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  • DOI: https://doi.org/10.1007/s11164-023-05038-y

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