Diphenyl-Substituted Triazine Derivatives: Synthesis, α-glucosidase Inhibitory Activity, Kinetics and In Silico Studies

Abstract

Background: Diabetes mellitus (DM) is a chronic disorder, considered to be a major global health challenge in the 21st century. α-Glucosidase enzyme is a well-known drug target to treat Type II DM. Methods: A new library of biphenyl-substituted triazines was synthesized and confirmed by various spectroscopic techniques. Results: All compounds showed potent α-glucosidase inhibitory activity, with IC₅₀ values ranging from 35.35 ± 0.34 to 564.41 ± 0.91 μM, as the standard acarbose, IC₅₀ value of 750.7 ± 0.13 μM. Our in silico study has predicted key interactions with the enzyme's active site. Drug-likeness and absorption, distribution, metabolism, excretion and toxicity were also studied. Conclusion: This study has identified a range of potential hits against the α-glucosidase enzyme that may serve as antidiabetic agents after further investigations.

Graphical Abstract

Keywords:

• α-glucosidase inhibitors
• competitive inhibitor
• diabetes mellitus
• in silico studies
• triazine

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Author contributions

S Shamim: synthesis, characterization, conceptualization, methodology, spectroscopic data analysis of synthesized compounds, and writing of the original draft. M Mahdavi and M Mohammadi-Khanaposhtani: investigation of biological experiments and kinetics studies. N Ullah: conceptualization, investigation, writing – review and editing – of the final manuscript draft. U Salar and M Ali: quality control, characterization of spectra and final review of the manuscript. MA Faramarzi: investigation of molecular docking studies. M Taha: software, validation and visualization. KM Khan: supervision, conceptualization, visualization, resources, project administration, methodology, investigation, funding acquisition, formal analysis, review, editing and validation of the final draft of the manuscript. All authors revised and approved the final draft and data analysis. All authors have read and agreed to the published version of the manuscript.

Financial & competing interests disclosure

The authors acknowledge the financial support of the Sindh Higher Education Commission (SHEC), Pakistan, vide letter no.: NO.DD/SHEC/1-14/2014, project code: SHEC/SRSP/Med-3/15/2021-21. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.