Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Biological Evaluation of 9-(1H-Indol-3-Yl) Xanthen-4-(9H)-Ones Derivatives As Noncompetitive Α-Glucosidase Inhibitors: Kinetics and Molecular Mechanisms Publisher



Nourisefat M1 ; Salehi N1 ; Yousefinejad S2 ; Panahi F3 ; Bagherzadeh K4 ; Amanlou M5 ; Khalafinezhad A6 ; Karimijafari MH1 ; Sheibani N7 ; Moosavimovahedi AA1, 8
Authors

Source: Structural Chemistry Published:2019


Abstract

The α-Glucosidase plays a key role in attenuation of postprandial hyperglycemia in diabetic patients. In this study, a class of 9-(1H-Indol-3-yl) xanthen-4-(9H)-ones derivatives (M1-M20) were evaluated for their α-Glucosidase inhibitory activity. The inhibitory activities of these compounds were evaluated via inhibition kinetics, molecular dynamic (MD) simulations, ensemble docking, and linear quantitative structure–activity relationship (QSAR) models. The results from the serial kinetic studies demonstrated that most of the ligands could directly inactivate enzyme activity in a dose-dependent manner. A typical non-competitive type of inhibition was observed, with compound M15 showing the highest inhibitory activity among the ligands tested. Also, MD simulations and ensemble docking studies on α-glucosidase homology model confirmed the non-competitive inhibition mechanism. The best binding mode for these inhibitors and efficacy of hydrogen bonds and hydrophobic interactions on inhibitory activities of synthetic ligands were also disclosed. The QSAR studies showed that the electronegative and oxygen-containing functional groups of indolyl-xanthone structures play a significant role in low-to-moderate inhibitory properties of these potentially anti-diabetic drugs against α-Glucosidase enzyme. Thus, our studies provide important molecular mechanisms delineating α-Glucosidase inhibition, which could aid in development of new drugs for type 2 diabetes mellitus treatment. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Related Docs
View other Related Docs
1. Heterocyclic Compounds: Effective Α-Amylase and Α-Glucosidase Inhibitors, Current Topics in Medicinal Chemistry (2017)
2. Synthesis and Biological Evaluation of 2-(2-Methyl-1H-Pyrrol-3-Yl)-2-Oxo-N-(Pyridine-3-Yl) Acetamide Derivatives: In Vitro Α-Glucosidase Inhibition, and Kinetic and Molecular Docking Study, Chemical Papers (2020)
3. Study on the Interaction of Triaryl-Dihydro-1,2,4-Oxadiazoles With Α-Glucosidase, DARU# Journal of Pharmaceutical Sciences (2020)
Experts (# of related papers)
View all Related Experts
Mohammad Ali Faramarzi (15)
Mohammad Mahdavi (13)
Other Related Docs
4. Design, Synthesis, and Investigation of Novel 5-Arylpyrazole-Glucose Hybrids As Α-Glucosidase Inhibitors, Scientific Reports (2025)
5. Study on the Interaction of 1,5-Diaryl Pyrrole Derivatives With Αglucosidase; Synthesis, Molecular Docking, and Kinetic Study, Medicinal Chemistry (2021)
6. Design, Synthesis Docking and Molecular Dynamics Studies of 2-Amino-4-Phenylthiazole-Indole Hybrids As Α-Glucosidase Inhibitors, Journal of Molecular Structure (2024)
7. Synthesis and Structure–Activity Relationship Studies of Benzimidazole-Thioquinoline Derivatives As Α-Glucosidase Inhibitors, Scientific Reports (2023)
8. New Phenylthiosemicarbazide-Phenoxy-1,2,3-Triazole-N-Phenylacetamides As Dual Inhibitors Against Α-Glucosidase and Ptp-1B for the Treatment of Type 2 Diabetes, Archiv der Pharmazie (2024)
9. Design, Synthesis, and Molecular Docking Studies of Diphenylquinoxaline-6-Carbohydrazide Hybrids As Potent Α-Glucosidase Inhibitors, BMC Chemistry (2022)
10. Synthesis, in Vitro Evaluation, and Molecular Docking Studies of Novel Hydrazineylideneindolinone Linked to Phenoxymethyl-1,2,3-Triazole Derivatives As Potential Α-Glucosidase Inhibitors, Bioorganic Chemistry (2021)
11. Benzoylquinazolinone Derivatives As New Potential Antidiabetic Agents: Α-Glucosidase Inhibition, Kinetic, and Docking Studies, Journal of the Chinese Chemical Society (2020)
12. Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia, Scientific Reports (2025)
13. Ugi Four-Multicomponent Reaction Based Synthesis, in Vitro, and in Silico Enzymatic Evaluations of New Pyrazino[1,2-A]Indole-1,4-Dione-Indole-2-Phenylacetamides As Potent Inhibitors Against Α-Glucosidase and Α-Amylase, Chemistry and Biodiversity (2024)
14. Synthesis, in Vitro and in Silico Enzymatic Inhibition Assays, and Toxicity Evaluations of New 4,5-Diphenylimidazole-N-Phenylacetamide Derivatives As Potent Α-Glucosidase Inhibitors, Medicinal Chemistry Research (2021)
15. Pyrano[2,3-B]Chromone Derivatives As Novel Dual Inhibitors of Α-Glucosidase and Α-Amylase: Design, Synthesis, Biological Evaluation, and in Silico Studies, Bioorganic Chemistry (2024)
16. Design and Synthesis of Novel Quinazolinone-Pyrazole Derivatives As Potential Α-Glucosidase Inhibitors: Structure-Activity Relationship, Molecular Modeling and Kinetic Study, Bioorganic Chemistry (2021)
17. Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor, Scientific Reports (2021)
18. The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes, Gut Pathogens (2021)
19. Rational Design of New Quinoline-Benzimidazole Scaffold Bearing Piperazine Acetamide Derivatives As Antidiabetic Agents, Bioorganic Chemistry (2024)
20. Novel Coumarin Containing Dithiocarbamate Derivatives As Potent Α-Glucosidase Inhibitors for Management of Type 2 Diabetes, Medicinal Chemistry (2021)