Skip to main content

Advertisement

SpringerLink
Log in

Benzoxazolyl linked benzylidene based rhodanine and analogs as novel antidiabetic agents: synthesis, molecular docking, and in vitro studies

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Benzoxazolyl linked meta- and para-substituted new chemical entities (5a–5h) featuring thiazolidinedione, rhodanine, hydantoin, and thiohydantoin moieties were synthesized and characterized by 1H NMR, 13C NMR, FT-IR, and HRMS spectral studies. In addition, all compounds were screened for α-glucosidase inhibitory activity and further supported by molecular docking studies carried out at the active site of α-glucosidase (PDB code: 3TOP) in comparison to acarbose used as a standard drug. Out of eight tested compounds, 5d was found as the most active inhibitor of α-glucosidase (IC50 = 9.48 ± 0.36 µM), having rhodanine moiety substituted at meta-position of the phenyl ring.

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

Scheme 1
Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cho NH, Shaw JE, Karuranga S, Haung YH, RochaFernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81. https://doi.org/10.1016/j.diabres.2018.02.023.

    Article  CAS  PubMed  Google Scholar 

  2. West IC. Radicals and oxidative stress in diabetes. Diabet Med. 2000;17:171–80. https://doi.org/10.1046/j.1464-5491.2000.00259.x.

    Article  CAS  PubMed  Google Scholar 

  3. Nguyen DV, Shawand LC, Grant MB. Inflammation in the pathogenesis of microvascular complications in diabetes. Front Endocrinol. 2012;3:170. doi: 10.3389%2Ffendo.2012.00170.

    Article  Google Scholar 

  4. Zachary T, Bloomgarden MD. Approaches to treatment of type 2 diabetes. Diabetes Care. 2008;8:1697–703. https://doi.org/10.2337/dc08-zb08.

    Article  Google Scholar 

  5. Chakrabarti R, Rajagopalan R. Diabetes and insulin resistance associated disorders: disease and the therapy. Curr Sci. 2002;83:1533–8. https://www.jstor.org/stable/24108177.

  6. Martin AE, Montogomery PA. Acarbose: an alpha-glucosidase inhibitor. Am J Health Syst Pharm. 1996;53:2277–90. https://doi.org/10.1093/ajhp/53.19.2277.

    Article  CAS  PubMed  Google Scholar 

  7. Khan MS, Munawar MA, Ashraf M, Alam U, Ata A, Asiri AM, et al. Synthesis of novel indenoquinoxaline derivatives as potent α-glucosidase inhibitors. Bioorg Med Chem. 2014;22:1195–200. https://doi.org/10.1016/j.bmc.2013.12.024.

    Article  CAS  PubMed  Google Scholar 

  8. Pili R, Chang J, Partis RA, Mueller RA, Chrest FJ, Passaniti A. The alpha-glucosidase I inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth. Cancer Res. 1995;55:2920–6. https://pubmed.ncbi.nlm.nih.gov/7540952/.

  9. Mehta A, Zitzmann N, Rudd PM, Block TM, Dwek RA. Alpha-glucosidase inhibitors as potential broad-based anti-viral agents. FEBS Lett. 1998;430:17–22. https://doi.org/10.1016/s0014-5793(98)00525-0.

    Article  CAS  PubMed  Google Scholar 

  10. Zitzmann N, Mehta AS, Carrouee S, Butters TM, Platt FM, McCauley J, et al. Imino sugars inhibit the formation and secretion of bovine viral diarrhea virus, a pestivirus model of hepatitis C virus: implications for the development of broad spectrum anti-hepatitis virus agents. Proc Natl Acad Sci USA. 1999;96:11878–82. https://doi.org/10.1073/pnas.96.21.11878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chinthala Y, Domatti AK, Sarfaraz A, Singh SP, Arigari NK, Gupta N, et al. Synthesis, biological evaluation and molecular modeling studies of some novel thiazolidinediones with triazole ring. Eur J Med Chem. 2013;70:308–14. https://doi.org/10.1016/j.ejmech.2013.10.005.

    Article  CAS  PubMed  Google Scholar 

  12. Wang G, Peng Y, Xie Z, Wang J, Chen M. Synthesis, α-glucosidase inhibition and molecular docking studies of novel thiazolidine-2,4-dione or rhodanine derivatives. Med Chem Commun. 2017;8:1477–84. https://doi.org/10.1039/C7MD00173H.

    Article  CAS  Google Scholar 

  13. Wang G, Peng Z, Wang J, Li J, Li X. Synthesis, biological evaluation and molecular docking study of N-arylbenzo[d]oxazol-2-amines as potential α-glucosidase inhibitors. Bioorg Med Chem. 2016;24:5374–9. https://doi.org/10.1016/j.bmc.2016.08.061.

    Article  CAS  PubMed  Google Scholar 

  14. Singh G, Singh A, Verma RK, Mall R, Azeem U. Synthesis, biological evaluation and molecular docking studies of novel benzimidazole derivatives. Comp Biol Chem. 2018;72:45–52. https://doi.org/10.1016/j.compbiolchem.2017.12.010.

    Article  CAS  Google Scholar 

  15. Singh V, Singh A, Singh G, Verma RK, Mall R. Novel benzoxazole derivatives featuring rhodanine and analogs as antihyperglycemic agents: synthesis, molecular docking, and biological studies. Med Chem Res. 2018;27:735–43. https://doi.org/10.1007/s00044-017-2097-1.

    Article  CAS  Google Scholar 

  16. Kaur J, Singh A, Singh G, Verma RK, Mall R. Novel indolyl linked para-substituted benzylidene-based phenyl containing thiazolidinediones and their analogs as α-glucosidase inhibitors: synthesis, in vitro and molecular docking studies. Med Chem Res. 2018;27:903–14. https://doi.org/10.1007/s00044-017-2112-6.

    Article  CAS  Google Scholar 

  17. Martínez-López D, Yu ML, García-Iriepa C, Campos PJ, Frutos ML, Golen JA, et al. Hydantoin-based molecular photoswitches. J Org chem. 2015;80:3929–39. https://doi.org/10.1021/acs.joc.5b00244.

    Article  PubMed  Google Scholar 

  18. Toubal K, Djafri A, Chouaih A, Talbi A. Synthesis and structural determination of novel 5-arylidene-3-N(2-alkyloxyaryl)-2-thioxothiazolidin-4-ones. Molecules. 2012;17:3501–9. https://doi.org/10.3390/molecules17033501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ishida T, In Y, Inoue M, Ueno Y, Tanaka C, Hamanaka N. Structural elucidation of epalrestat (ONO-2235), a potent aldose reductase inhibitor, and isomerization of its double bonds. Tetrahedron Lett. 1989;30:959–62. https://doi.org/10.1016/S0040-4039(00)95290-0.

    Article  CAS  Google Scholar 

  20. Lazer ES, Miao CK, Wong HC, Sorcek R, Spero DM, Gilman A, et al. Benzoxazolamines and benzothiazolamines: potent, enantioselective inhibitors of leukotriene biosynthesis with a novel mechanism of action. J Med Chem. 1994;37:913–23. https://doi.org/10.1021/jm00033a008.

    Article  CAS  PubMed  Google Scholar 

  21. Mall R, Singh A, Singh G, Singh V, Verma RK. Indolyl linked meta‐substituted benzylidenes as novel ligands: synthesis, biological evaluation, and molecular docking studies. J Heterocycl Chem. 2019;56:1542–52. https://doi.org/10.1002/jhet.3529.

    Article  CAS  Google Scholar 

  22. Granfeldt Y, Bjorck I, Drews A, Tovar J. An in vitro procedure based on chewing to predict metabolic response to starch in cereal and legume products. Eur J Clin Nutr. 1992;46:649–60. https://pubmed.ncbi.nlm.nih.gov/1396482/.

Download references

Acknowledgements

The authors are highly thankful to Punjabi University Patiala authorities for providing the necessary research facilities. The authors also submit their sincere thanks to the Director and Mr. Avtar Singh of Sophisticated Analytical Instrumentation Facility (SAIF), Panjab University, Chandigarh, for extending facilities for spectral analysis. Furthermore, VS acknowledges the University Grants Commission (UGC) for providing the Maulana Azad National Fellowship (Award number: MANF-2015-17-PUN-60098).

Author information

Authors and Affiliations

  1. Synthetic Organic and Medicinal Chemistry Laboratory, Department of Chemistry, Punjabi University, Patiala, 147002, Punjab, India

    Varinder Singh, Amanjot Singh, Gagandeep Singh & Raman K. Verma

  2. Department of Basic and Applied Sciences, Punjabi University, Patiala, 147002, Punjab, India

    Rajiv Mall

Authors
  1. Varinder Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amanjot Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gagandeep Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raman K. Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rajiv Mall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajiv Mall.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, V., Singh, A., Singh, G. et al. Benzoxazolyl linked benzylidene based rhodanine and analogs as novel antidiabetic agents: synthesis, molecular docking, and in vitro studies. Med Chem Res 30, 1905–1914 (2021). https://doi.org/10.1007/s00044-021-02781-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-021-02781-y

Keywords

Search

Navigation