Skip to main content
SpringerLink
Log in

In vivo and in silico evaluations of a synthetic pyrano[3,2-c]quinoline derivative as a potent anti-diabetic agent

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Background

The in vivo assessment of a novel compound is a pivotal step in the development of a new drug. In this study, we selected 1-(2-bromophenyl)-1,11-dihydro-3H-benzo[h]pyrano[3,2-c]quinoline-3,12(2H)-dione (2-BDBPQD), identified as an exemplary α-glucosidase inhibitor in preliminary in vitro assays, for further evaluation in an in vivo anti-diabetic context.

Methods

The in vivo anti-diabetic effect of 2-BDBPQD was assessed using a streptozotocin (STZ)-induced diabetic Wistar rat model. Recognizing the relevance of lipid factors in diabetes, we also investigated the impact of this compound on the lipid profile of diabetic Wistar rats. In silico studies, encompassing docking studies and pharmacokinetic predictions of 2-BDBPQD, were conducted.

Results

The results obtained indicated a significant reduction in blood glucose levels with 2-BDBPQD treatment compared to acarbose. However, no significant effects on the lipid profile were observed. In silico studies revealed that 2-BDBPQD interacted with key residues in the α-glucosidase active site and exhibited favorable pharmacokinetic properties.

Conclusion

In summary, the study demonstrated the in vivo anti-hyperglycemic activity of 2-BDBPQD. Nevertheless, further in vivo evaluations are recommended to comprehensively assess its potential as a new drug for the treatment of diabetes.

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

Abbreviations

DM:

Diabetes mellitus

T1DM:

Type 2 diabetes mellitus

T1DM:

Type 2 diabetes mellitus

SGLT2:

Sodium/glucose cotransporter 2

2-BDBPQD:

1-(2-bromophenyl)-1,11-dihydro-3H-benzo[h]pyrano[3,2-c]quinoline-3,12(2H)-dione

STZ:

Streptozotocin

BGL:

Blood glucose level

LDL:

Low-density lipoprotein

HDL:

High-density lipoprotein

BBB:

Blood brain barrier

HIA:

Human intestinal absorption

References

  1. Lotfy M, Adeghate J, Kalasz H, Singh J, Adeghate E. Chronic complications of diabetes mellitus: a mini review. Curr Diabetes Rev. 2017;13(1):3–10.

    Article  PubMed  CAS  Google Scholar 

  2. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol. 2019;11(3):45.

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Leon BM, Maddox TM. Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mukhtar Y, Galalain A, Yunusa U. A modern overview on diabetes mellitus: a chronic endocrine disorder. Eur J Biol Biotechnol. 2020;5(2):1–4.

    Google Scholar 

  5. Whalen K, Miller S, Onge ES. The role of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes. Clin Ther. 2015;37(6):1150–66.

    Article  PubMed  CAS  Google Scholar 

  6. Corder AM, Henry RJ. Carbohydrate-degrading enzymes in germinating wheat. Cereal Chem. 1989;66(5):435–9.

    CAS  Google Scholar 

  7. Eldor R, DeFronzo RA, Abdul-Ghani M. In vivo actions of peroxisome proliferator–activated receptors: glycemic control, insulin sensitivity, and insulin secretion. Diabetes Care. 2013;36(Supplement_2):S162–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Chiba S. Molecular mechanism in α-glucosidase and glucoamylase. Biosci Biotechnol Biochem. 1997;61(8):1233–9.

    Article  PubMed  CAS  Google Scholar 

  9. Wu B, Yan J, Yang J, Xia Y, Li D, Zhang F, Cao H. Extension of the life span by Acarbose: is it mediated by the gut microbiota? Aging Dis. 2022;13(4):1005.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mohammadi-Khanaposhtani M, Nori M, Valizadeh Y, Javanshir S, Dastyafteh N, Moaazam A, Hosseini S, Larijani B, Adibi H, Biglar M, Hamedifar H. New 4-phenylpiperazine-carbodithioate-N-phenylacetamide hybrids: synthesis, in vitro and in silico evaluations against cholinesterase and α-glucosidase enzymes. Arch Pharm. 2022;355(5):2100313.

    Article  CAS  Google Scholar 

  11. Nikookar H, Mohammadi-Khanaposhtani M, Imanparast S, Faramarzi MA, Ranjbar PR, Mahdavi M, Larijani B. Design, synthesis and in vitro α-glucosidase inhibition of novel dihydropyrano [3, 2-c] quinoline derivatives as potential anti-diabetic agents. Bioorg Chem. 2018;77:280–6.

    Article  PubMed  CAS  Google Scholar 

  12. Lee BH, Lee CC, Wu SC. Ice plant (Mesembryanthemum crystallinum) improves hyperglycaemia and memory impairments in a Wistar rat model of streptozotocin-induced diabetes. J Sci Food Agric. 2014;94(11):2266–73.

    Article  PubMed  CAS  Google Scholar 

  13. Chinthala Y, Thakur S, Tirunagari S, Chinde S, Domatti AK, Arigari NK, Srinivas KV, Alam S, Jonnala KK, Khan F, Tiwari A. Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity. Eur J Med Chem. 2015;93:564–73.

    Article  PubMed  CAS  Google Scholar 

  14. Seul SC. Bioinformatics and Molecular Design Research Center. PreADMET program. 2004. http://preadmet.bmdrc.org.

  15. Noori M, Davoodi A, Iraji A, Dastyafteh N, Khalili M, Asadi M, Mohammadi Khanaposhtani M, Mojtabavi S, Dianatpour M, Faramarzi MA, Larijani B. Design, synthesis, and in silico studies of quinoline-based-benzo [d] imidazole bearing different acetamide derivatives as potent α-glucosidase inhibitors. Sci Rep. 2022;12(1):14019.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Noori M, Rastak M, Halimi M, Ghomi MK, Mollazadeh M, Mohammadi-Khanaposhtani M, Sayahi MH, Rezaei Z, Mojtabavi S, Faramarzi MA, Larijani B. Design, synthesis, in vitro, and in silico enzymatic evaluations of thieno [2, 3-b] quinoline-hydrazones as novel inhibitors for α-glucosidase. Bioorg Chem. 2022;127:105996.

    Article  PubMed  CAS  Google Scholar 

  17. Taj S, Ahmad M, Ashfaq UA. Exploring of novel 4-hydroxy-2H-benzo [e][1, 2] thiazine-3-carbohydrazide 1, 1-dioxide derivative as a dual inhibitor of α-glucosidase and α-amylase: molecular docking, biochemical, enzyme kinetic and in-vivo mouse model study. Int J Biol Macromol. 2022;207:507–21.

    Article  PubMed  CAS  Google Scholar 

  18. Khan HA, Sobki SH, Khan SA. Association between glycaemic control and serum lipids profile in type 2 diabetic patients: HbA 1c predicts dyslipidaemia. Int J Clin Exp Med. 2007;7:24–9.

    CAS  Google Scholar 

Download references

Acknowledgments

The ethics code for this work is IR. IAU. AMOL. REC. 1400.010. Furthermore, the authors thankfully acknowledge the scientific support provided by Research and Technology Empowerment Committee of Babol University of Medical Science.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran

    Nafiseh Zare

  2. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, University of Medical Sciences, Tehran, Iran

    Fatemeh Bandarian & Ensieh Nasli Esfahani

  3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Bagher Larijani & Mohammad Mahdavi

  4. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Maryam Mohammadi-Khanaposhtani & Hossein Najafzadehvarzi

Authors
  1. Nafiseh Zare
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatemeh Bandarian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ensieh Nasli Esfahani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bagher Larijani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Mahdavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maryam Mohammadi-Khanaposhtani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hossein Najafzadehvarzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Maryam Mohammadi-Khanaposhtani or Hossein Najafzadehvarzi.

Ethics declarations

Conflict of interest

The authors declared no conflict of interest in this study.

Additional information

Publisher’s Note

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

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

Zare, N., Bandarian, F., Esfahani, E.N. et al. In vivo and in silico evaluations of a synthetic pyrano[3,2-c]quinoline derivative as a potent anti-diabetic agent. J Diabetes Metab Disord (2023). https://doi.org/10.1007/s40200-023-01355-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40200-023-01355-6

Keywords

Search

Navigation