Diphenyl-substituted triazine derivatives: synthesis, α-glucosidase inhibitory activity, kinetics and in silico studies

Author:

Shamim Shahbaz1ORCID,Khan Khalid Mohammed12ORCID,Ali Muhammad1,Mahdavi Mohammad3,Salar Uzma4ORCID,Mohammadi-Khanaposhtani Maryam5,Faramarzi Mohammad Ali6,Ullah Nisar7,Taha Muhammad2ORCID

Affiliation:

1. HEJ Research Institute of Chemistry, International Center for Chemical & Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

2. Department of Clinical Pharmacy, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, PO Box 31441, Dammam, Saudi Arabia

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

4. Dr. Panjwani Center for Molecular Medicine & Drug Research, International Center for Chemical & Biological Sciences, University of Karachi, Karachi-75270, Pakistan

5. Cellular & Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

7. Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran, 31261, Saudi Arabia

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.

Funder

Sindh Higher Education Commission (SHEC), Pakistan

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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