Journal of PhytoPharmaceutical and Advanced Chemistry
Short Name: JPPAC• ISSN: 3139-9266• Peer-Reviewed Open Access
Computational Study of Alkaloids Targeting O-GlcNAc Transferase as Antidiabetic Agents
Abstract
O-GlcNAc Transferase (OGT) plays a pivotal role in glucose metabolism and insulin signaling, making it an attractive therapeutic target for the management of diabetes mellitus. In the present study, a comprehensive in silico approach was employed to investigate the inhibitory potential of selected alkaloids against human OGT, with an emphasis on their binding affinity and pharmacokinetic suitability. Molecular docking analysis was performed using AutoDock Vina to elucidate the interaction patterns between the selected compounds and the active site of OGT. The docking results revealed that berberine exhibited the strongest binding affinity (−7.8 kcal/mol), slightly surpassing that of the native ligand (−7.7 kcal/mol), and formed stable hydrogen bonding and hydrophobic interactions with key catalytic residues such as LYS898, ASN838, and PRO559. In contrast, castanospermine and swainsonine showed comparatively weaker binding affinities, attributed to limited interaction networks within the binding pocket. To further assess the drug development potential of the studied compounds, in silico ADMET analysis was carried out using SwissADME and ADMETlab 3.0. Berberine demonstrated favorable physicochemical properties, superior drug-likeness (highest QED score), and acceptable absorption and toxicity profiles compared to the native ligand and other alkaloids. Although potential cytochrome P450 interactions and moderate bioaccumulation were predicted for berberine, its overall pharmacokinetic profile was well balanced. Collectively, the integrated docking and ADMET results highlight berberine as a promising lead alkaloid targeting OGT, warranting further in vitro and in vivo validation for its potential development as an antidiabetic agent.
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Cited References
- 01.
1. Sanhueza L, Durruty P, Vargas C, Vignolo P, Elgueta K. Diabetes Mellitus: A Group of Genetic-Based Metabolic Diseases. In: Cellular Metabolism and Related Disorders. Diabetes Care. 2009 Jan; 32(Suppl 1):S62–S67. doi: 10.2337/dc09-S062.
- 02.
2. Piero MN, Makenzi N, Njagi J. Diabetes mellitus – a devastating metabolic disorder. Asian J Biomed Pharm Sci. 2015;4(40):1–7. doi: 10.15272/ajbps.v4i40.645
- 03.
3. Grunberger G. Should Side Effects Influence the Selection of Antidiabetic Therapies in Type 2 Diabetes?. Curr Diab Rep. 2017 Apr;17(4):21. doi: 10.1007/s11892-017-0853-8.
- 04.
4. Issad T, Masson E, Pagesy P. O-GlcNAc glycosylation, signalisation de l’insuline et complications diabétiques. Diabetes Metab. 2010;36(6):423–35. doi: 10.1016/j.diabet.2010.09.001.
- 05.
5. Bauer C, Göbel K, Nagaraj N, Colantuoni C, Wang M, Müller U, et al. Phosphorylation of TET proteins is regulated via O-GlcNAcylation by the O-Linked N-Acetylglucosamine transferase (OGT). J Biol Chem. 2015;290(8):4801–12. doi: 10.1074/jbc.M114.605881.
- 06.
6. She N, Zhao Y, Hao J, Xie S, Wang C. Uridine diphosphate release mechanism in O-N-acetylglucosamine (O-GlcNAc) transferase catalysis. Biochim Biophys Acta - Gen Subj. 2019;1863(3):609–22. doi: 10.1016/j.bbagen.2018.12.005.
- 07.
7. Hart GW. Three decades of research on O-GlcNAcylation - A major nutrient sensor that regulates signaling, transcription and cellular metabolism. Front Endocrinol (Lausanne). 2014;5(OCT) 27:5:183. doi: 10.3389/fendo.2014.00183.
- 08.
8. Dong W, Imdad L, Xu S, Wang Y, Liu C, Song S, et al. O-GlcNAc Modification Is a Promising Therapeutic Target for Diabetic Retinopathy. Int J Mol Sci. 2024;25(11):6286. doi: 10.3390/ijms25116286.
- 09.
9. Zhang N, Jiang H, Zhang K, Zhu J, Wang Z, Long Y, et al. OGT as potential novel target: Structure, function and inhibitors. Vol. 357, Chemico-Biological Interactions. 2022 Apr 25:357:109886. doi: 10.1016/j.cbi.2022.109886.
- 10.
10. Toma L, Deleanu M, Sanda GM, Barbălată T, Niculescu LŞ, Sima AV, et al. Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders. Vol. 25, International Journal of Molecular Sciences. 2024 Apr 9;25(8):4162. doi: 10.3390/ijms25084162.
- 11.
11. Mehdi S, Mehmood MH, Ahmed MG, Ashfaq UA. Antidiabetic activity of Berberis brandisiana is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats. Front Pharmacol. 2023;14:1085013. doi: 10.3389/fphar.2023.1085013.
- 12.
12. Dasari V, Shaikh A, Sisodiya D, Bhargava T, Dangi R, Nagwe S, et al. Stability Study of Mucoadhesive Microsphere Containing Nateglinide by Using Biodegradable Polymer Chitosan. J Pharm Res Int. 2021;866–72. doi: 10.9734/jpri/2021/v33i47A33086
- 13.
13. Benhamed F, Filhoulaud G, Caron S, Lefebvre P, Staels B, Postic C. O-GlcNAcylation links ChREBP and FXR to glucose-sensing. Vol. 5, Frontiers in Endocrinology. 2015 Jan 13:5:230. doi: 10.3389/fendo.2014.00230.
- 14.
14. Liu Y, Ren Y, Cao Y, Huang H, Wu Q, Li W, et al. Discovery of a Low Toxicity O-GlcNAc Transferase (OGT) Inhibitor by Structure-based Virtual Screening of Natural Products. Sci Rep. 2017;7(1) :12334. doi: 10.1038/s41598-017-12522-0.
- 15.
15. Shaheen A, Fida H, Akhmedov S, Rasulbek E, Ataullaev Z. In Silico Study of Alkaloids as Potential Cyclin-Dependent Kinase (CDK) Inhibitors. J Pharm Sci Comput Chem. 2025;1(4):324–35. doi; 10.48309/jpscc.2025.558357.1033.
- 16.
16. Khan SL, Sonwane GM, Siddiqui F, Jain SP. Discovery of Naturally Occurring Flavonoids as Human Cytochrome P450 (CYP3A4) Inhibitors with the Aid of Computational Chemistry. Indo Global J Pharmaceutical Sci. 2020; 10(4): 58-69. doi: 10.35652/IGJPS.2020.10409.
- 17.
17. Jadhav PB, Jadhav SB, Zehravi M, Mubarak MS, Islam F, Jeandet P, et al. Virtual Screening, Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors. Molecules. 2023;28(1):149. doi: 10.3390/molecules28010149.
- 18.
18. Suryawanshi RM, Shimpi RB, Muralidharan V, Nemade LS, Gurugubelli S, Baig S, et al. ADME, Toxicity, Molecular Docking, Molecular Dynamics, Glucokinase activation, DPP-IV, α-amylase, and α-glucosidase Inhibition Assays of Mangiferin and Friedelin for Antidiabetic Potential. Chem Biodivers. 2025 Dec;22(5):e202402738. doi: 10.1002/cbdv.202402738.
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Journal of PhytoPharmaceutical and Advanced Chemistry
An international, peer-reviewed journal integrating phytopharmaceutical sciences, natural products, and advanced pharmaceutical chemistry.
This peer-reviewed publication is indexed directly from the publisher repository adhering to Open Archives Initiative (OAI-PMH) metadata standards, Crossref DOI schema, and Google Scholar Highwire Press protocols.