Skip to main content
SpringerLink
Log in

Meteloxetin (1) Novel Phenolic Amino-Oxetane Cholinesterase Inhibitors from Datura metel Linn and First-Principle Investigations

  • Research Article-Chemistry
  • Published:
Arabian Journal for Science and Engineering Aims and scope Submit manuscript

Abstract

Meteloxetin (1), a new phenolic amino-oxetane, and eight known new source phenols (2–9) have been bioassay-directed isolated from methanolic extract of Datura metel Linn. Their structures were elucidated through modern spectroscopic data. The plant extract showed the significant inhibition potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and its dichloromethane (DCM) fraction exhibited the remarkable inhibition potentials against AChE with IC50 (inhibition concentration) value 1.32 ± 0.02 µg/ml and BChE with IC50 value 1.13 ± 0.01 µg/ml, when compared with the standard drug eserine (AChE, IC50 0.04 ± 0.01 µg/ml) and galanthamine (BChE, IC50 0.92 ± 0.01 µg/ml). The bioactive DCM fraction was subjected to systematic isolation protocol to isolate the 1–9 compounds, and all were subjected to evaluate their AChE and BChE inhibition potentials. From these isolates, compound 1 showed the effective inhibition potential against BChE with IC50 value 0.84 ± 0.03 µg/ml and excellent inhibition potential against AChE with IC50 value 0.07 ± 0.02 µg/ml. This strong inhibition potential of 1 is due to the presence of amino-oxetane groups in it. The in silico studies indicate that oxetane rings contain high-energy oxygen, which makes it a marvelous pharmacophore with diverse biological potentials. The potent nature of compound 1 has also been evaluated by exploring its electronic properties, molecular electrostatic potential and Hirshfeld analysis by density functional theory.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ekor, M.: The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front. Pharm. 4, 177 (2014)

    Article  Google Scholar 

  2. Newman, D.J.; Cragg, G.M.: Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 79(3), 629–661 (2016)

    Article  Google Scholar 

  3. Babalola, S.; Sulaiman, M.; Hassan, A.; Adawa, D.: Evaluation of the crude methanolic seed extract of datura metel l. As a potential oral anaesthetic in dogs. Vet. Res. 6, 115–119 (2013)

    Google Scholar 

  4. Jamdhade, M.; Survase, S.; Kare, M.; Bhuktar, A.: Phytochemical studies on datura metel linn. In marathwada region, maharashtra. J. Phytol. 2(12), 46–48 (2010)

    Google Scholar 

  5. Muthusamy, A.; Punitha, M.; Beslin, L.G.: Phytochemical screening of Datura metel Linn and its antimicrobial activity on selected human pathogens. Int. J. Bioassays 3(11), 3474–3478 (2014)

    Google Scholar 

  6. Sangeetha, S.; Deepa, M.; Sugitha, N.; Mythili, S.; Sathiavelu, A.: Antioxidant activity and phytochemical analysis of Datura metel. Int. J. Drug Dev. Res. 6(4), 46–53 (2014)

    Google Scholar 

  7. Liu, Y.; Guan, W.; Yang, C.-L.; Luo, Y.-M.; Liu, Y.; Zhou, Y.-Y.; Liu, L.-N.; Yang, B.-Y.; Kuang, H.-X.: Steroids with potential anti-inflammatory activity from the roots of datura metel l. Can. J. Chem. 98(2), 74–78 (2020)

    Article  Google Scholar 

  8. Tan, J.-Y.; Liu, Y.; Cheng, Y.-G.; Sun, Y.-P.; Pan, J.; Yang, S.-H.; Kuang, H.-X.; Yang, B.-Y.: Anti-inflammatory sesquiterpenoids from the leaves of Datura metel L. Fitoterapia 142, 104531 (2020)

    Article  Google Scholar 

  9. Yang, B.-Y.; Jiang, H.-B.; Liu, Y.; Chen, J.; Kuang, H.-X.: Steroids from the seeds of datura metel. J. Asian Nat. Prod. Res. 22(3), 257–263 (2018)

    Article  Google Scholar 

  10. Srivastava, N.; Chauhan, A.; Sharma, B.: Isolation and characterization of some phytochemicals from Indian traditional plants. Biotech. Res. Int. 549850, 1–8 (2012)

    Article  Google Scholar 

  11. Srivastava, N.; Sharma, R.; Singh, N.; Sharma, B.: Acetylcholinesterase from human erythrocytes membrane: a screen for evaluating the activity of some traditional plant extracts. Cell. Mol. Biol. 58(1), 160–169 (2012)

    Google Scholar 

  12. Lateef, M.; Azhar, A.; Siddiqui, B.S.; Zarina, S.; Anwar, M.F.; Siddiqui, K.; Azhar, K.F.; Iqbal, L.; Mehmood, R.; Perveen, S.: New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, in vitro and in silico studies. Heliyon 3(7), e00350 (2017)

    Article  Google Scholar 

  13. Lolak, N.; Boga, M.; Tuneg, M.; Karakoc, G.; Akocak, S.; Supuran, C.T.: Sulphonamides incorporating 1, 3, 5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile. J. Enzyme Inhib. Med. Chem. 35(1), 424–431 (2020)

    Article  Google Scholar 

  14. Mehta, M.; Adem, A.; Sabbagh, M.: New acetylcholinesterase inhibitors for alzheimer’s disease. Inter. J. Alzheimer’s Dis (2012). https://doi.org/10.1155/2012/728983

    Article  Google Scholar 

  15. Imran, M.; Irfan, A.; Ibrahim, M.; Assiri, M.A.; Khalid, N.; Ullah, S.; Al-Sehemi, A.G.: Carbonic anhydrase and cholinesterase inhibitory activities of isolated flavonoids from oxalis corniculata l. And their first-principles investigations. Ind. Crops Prod. 148, 112285 (2020)

    Article  Google Scholar 

  16. Ibach, B.; Haen, E.: Acetylcholinesterase inhibition in alzheimer’s disease. Current Pharmaceut. Design 10(3), 231–251 (2004)

    Article  Google Scholar 

  17. Mukherjee, P.K.; Kumar, V.; Mal, M.; Houghton, P.J.: Acetylcholinesterase inhibitors from plants. Phytomedicine 14(4), 289–300 (2007)

    Article  Google Scholar 

  18. Ellman, G.L.; Courtney, K.D.; Andres Jr., V.; Featherstone, R.M.: A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharm. 7(2), 88–95 (1961)

    Article  Google Scholar 

  19. Demirtaş, G.; Dege, N.; Ağar, E.; Şahin, S.: The crystallographic, spectroscopic and theoretical studies on (e)-2-[((4-fluorophenyl)imino)methyl]-4-nitrophenol and (e)-2-[((3-fluorophenyl)imino)methyl]-4-nitrophenol compounds. Iran. J. Chem. Chem. Engineer. 37(5), 55–65 (2018)

    Google Scholar 

  20. Irfan, A.; Imran, M.; et al.: Exploration of electronic nature and intrinsic mobility of 10-(1,3-dithiol-2-ylidene)anthracene based organic semiconductor materials. Optik 224, 165530 (2020)

    Article  Google Scholar 

  21. Irfan, A.; Al-Zeidaneen, F.K.; Ahmed, I.; Al-Sehemi, A.G.; Assiri, M.A.; Ullah, S.; Abbas, G.: Synthesis, characterization and quantum chemical study of optoelectronic nature of ferrocene derivatives. Bull. Mater. Sci. 43(1), 45 (2020)

    Article  Google Scholar 

  22. Khalil Warad, I.; Al-Nuri, M.; Ali, O.; Abu-Reidah, I.M.; Barakat, A.; Ben Hadda, T.; Zarrouk, A.; Radi, S.; Touzani, R.; Hicham, E.: Synthesis, physico-chemical, hirschfield surface and dft/b3lyp calculation of two new hexahydropyrimidine heterocyclic compounds. Iran. J. Chem. Chem. Eng. 38(4), 59–68 (2019)

    Google Scholar 

  23. Mikulski, D.; Eder, K.; Molski, M.: Quantum-chemical study on relationship between structure and antioxidant properties of hepatoprotective compounds occurring in cynara scolymus and silybum marianum. J. Theor. Comput. Chem. 13(01), 1450004 (2014)

    Article  Google Scholar 

  24. Najafi, M.; Naqvi, S.A.R.: Theoretical study of the substituent effect on the hydrogen atom transfer mechanism of the irigenin derivatives antioxidant action. J. Theor. Comput. Chem. 13(02), 1450010 (2014)

    Article  Google Scholar 

  25. Sadasivam, K.; Jayaprakasam, R.; Kumaresan, R.: A DFT study on the role of different oh groups in the radical scavenging process. J. Theor. Comput. Chem. 11(04), 871–893 (2012)

    Article  Google Scholar 

  26. Seif, N.; Farhadi, A.; Badri, R.; Kiasat, A.R.: An experimental and theoretical study on bicyclo-3,4-dihydropyrimidinone derivative: synthesis and DFT calculation. Iran. J. Chem. Chem. Eng. (2019). https://doi.org/10.30492/ijcce.2019.35673

    Article  Google Scholar 

  27. Irfan, A.; Assiri, M.; Al-Sehemi, A.G.: Exploring the optoelectronic and charge transfer performance of diaza[5]helicenes at molecular and bulk level. Org. Electron. 57, 211–220 (2018)

    Article  Google Scholar 

  28. Al-Sehemi, A.G.; Irfan, A.: Effect of donor and acceptor groups on radical scavenging activity of phenol by density functional theory. Arab. J. Chem. 10(Supplement 2), S1703–S1710 (2017)

    Article  Google Scholar 

  29. Omura, S.; Murata, M.; Imamura, N.; Iwai, Y.; Tanaka, H.; Furusaki, A.; Matsumoto, T.: Oxetin, a new antimetabolite from an actinomycete. J. Antibiot. 37(11), 1324–1332 (1984)

    Article  Google Scholar 

  30. Bull, J.A.; Croft, R.A.; Davis, O.A.; Doran, R.; Morgan, K.F.: Oxetanes: recent advances in synthesis, reactivity, and medicinal chemistry. Chem. Rev. 116(19), 12150–12233 (2016)

    Article  Google Scholar 

  31. Akhtar, M.N.; Lam, K.W.; Abas, F.; Ahmad, S.; Shah, S.A.A.; Choudhary, M.I.; Lajis, N.H.: New class of acetylcholinesterase inhibitors from the stem bark of knema laurina and their structural insights. Bioorg. Med. Chem. Lett. 21(13), 4097–4103 (2011)

    Article  Google Scholar 

  32. Vil, V.; Terent’ev, A.O.; Al Quntar, A.A.A.; Gloriozova, T.A.; Savidov, N.; Dembitsky, V.M.: Oxetane-containing metabolites: origin, structures, and biological activities. Appl. Microbiol. Biotechnol. 103(6), 2449–2467 (2019)

    Article  Google Scholar 

  33. Singh, P.K.; Silakari, O.: The current status of o-heterocycles: a synthetic and medicinal overview. Chem. Med. Chem. 13(11), 1071–1087 (2018)

    Article  Google Scholar 

  34. Geerlings, P.; De Proft, F.; Langenaeker, W.: Conceptual density functional theory. Chem. Rev. 103(5), 1793–1874 (2003)

    Article  Google Scholar 

  35. Vektariene, A.; Vektaris, G.; Svoboda, J.: A theoretical approach to the nucleophilic behavior of benzofused thieno [3,2-b] furans using dft and hf based reactivity descriptors. Arkivoc 7, 311–329 (2009)

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the support from the Deanship of Scientific Research at the King Khalid University for funding through the research groups program under Grant Number R.G.P.2/76/41.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia

    Muhammad Imran, Ahmad Irfan, Mohammed A. Assiri & Abdullah G. Al-Sehemi

  2. Division of Science and Technology, Department of Chemistry, University of Education, Township, Lahore, Pakistan

    Rashad Mehmood, Riaz Hussain, Salwa Abbas, Aneela Fareed & Muhammad Saleem

  3. Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia

    Ahmad Irfan

  4. Department of Chemistry, University of Gujrat, Gujrat, 50700, Pakistan

    Sajjad Hussain Sumrra

  5. Faculty of Pharmacy, University of Sargodha, Punjab, Pakistan

    Noreen Khalid

Authors
  1. Muhammad Imran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rashad Mehmood
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Riaz Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmad Irfan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sajjad Hussain Sumrra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Salwa Abbas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammed A. Assiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Noreen Khalid
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aneela Fareed
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Muhammad Saleem
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Abdullah G. Al-Sehemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Muhammad Imran or Ahmad Irfan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 27 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Imran, M., Mehmood, R., Hussain, R. et al. Meteloxetin (1) Novel Phenolic Amino-Oxetane Cholinesterase Inhibitors from Datura metel Linn and First-Principle Investigations. Arab J Sci Eng 46, 5681–5690 (2021). https://doi.org/10.1007/s13369-020-05237-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13369-020-05237-4

Keywords

Search

Navigation