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Journals / Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi / 2026 / Cilt: 13 Sayı: 1

Quantum Chemical Calculation And Molecular Docking Studies Of Coumarin Based Curcumins As α-Glucosidase Inhibitors

Kumarin Bazlı Kurkuminlerin α-Glukozidaz İnhibitörleri Olarak Kuantum Kimyasal Hesaplamaları ve Moleküler Yerleştirme Çalışmaları

Semiha Köprü(Erciyes Üniversitesi)0000-0002-2269-6980
Pages
165–178
Publication Date
2026-05-31
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The antidiabetic effects of curcumin-derived compounds are promising for future drug candidate molecules.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:This study aimed to investigate the physicochemical, structural, and electronic properties, and in silico assessment of molecular docking studies of six coumarin-based ethylcurcumin derivatives (C1-C6) as α-glucosidase inhibitors.
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Key Findings & Data:The ground state geometries and chemical reactivity parameters of the compounds were calculated using the Lee–Yang–Parr, B3LYP hybrid functional with 6-311 ++ G(2d, 2p) basis set through Density Functional Theory (DFT) approach using the Gaussian 09 W.
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Conclusion & Impact:The antidiabetic effects of curcumin-derived compounds are promising for future drug candidate molecules.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Kurkumin · Yoğunluk Fonksiyonel Teorisi · α-glukozidaz

Abstract

This study aimed to investigate the physicochemical, structural, and electronic properties, and in silico assessment of molecular docking studies of six coumarin-based ethylcurcumin derivatives (C1-C6) as α-glucosidase inhibitors. The ground state geometries and chemical reactivity parameters of the compounds were calculated using the Lee–Yang–Parr, B3LYP hybrid functional with 6-311 ++ G(2d, 2p) basis set through Density Functional Theory (DFT) approach using the Gaussian 09 W. In addition, HOMO-LUMO energy levels and molecular electrostatic potential (MEP) analysis were performed to identify electrophilic and nucleophilic reactive sites. The ADMET (absorption, distribution, metabolism, elimination, and toxicity) profiles and pharmacokinetic parameters of all compounds were predicted through in silico calculations using the SwissADME and Pro Tox-3.0 web servers. Molecular docking analysis was performed for all compounds against the target protein (PDB ID: 3A4A) using AutoDock Vina (version 1.5.7). The docking results revealed that all compounds ( C1-C6) exhibited strong interactions with the 3A4A receptor. Computational studies showed that compound C5 had the highest binding energy (-9.9 kcal/mol) in the molecular docking. Curcumin compounds, identified as having potential antidiabetic properties, exhibited higher binding energies against the 3A4A receptor than the reference compound acarbose, based on molecular docking analysis. The antidiabetic effects of curcumin-derived compounds are promising for future drug candidate molecules.

Özet

Bu çalışmada altı kumarin bazlı etil kurkumin türevlerinin (C1-C6) fizikokimyasal, yapısal ve elektronik özelliklerinin araştırılması ve in silico moleküler yerleştirme çalışmalarıyla α-glukozidaz inhibitörü olarak değerlendirilmesi amaçlanmıştır. Bileşiklerin temel durum geometrileri ve kimyasal reaktivite parametreleri, Gaussian 09 W'da, Yoğunluk Fonksiyonel Teorisi (DFT) yaklaşımı kullanılarak, standart baz seti 6-311 ++ G(2d,2p) sahip B3LYP hibrit fonksiyoneli kullanılarak hesaplanmıştır. Buna ek olarak , elektrofilik ve nükleofilik reaktif bölgeleri belirlemek için HOMO-LUMO enerji seviyeleri ve moleküler elektrostatik potansiyel (MEP) analizi gerçekleştirilmiştir. ADMET (emilim, dağıtım, metabolizma, eliminasyon ve toksisite) profili ve farmakokinetik parametreler, SwissADME ve ProTox-3.0 web sunucusu kullanılarak tüm bileşikler için tahmin edilmiştir. AutoDock Vina 1.5.7 kullanılarak, tüm bileşikler için PDB ID: 3A4A'ya karşı moleküler yerleştirme analizi gerçekleştirilmiştir. Yapılan moleküler yerleştirme çalışmaları sonucunda, C1-C6 bileşikleri 3A4A reseptörü ile güçlü etkileşimler ortaya koymuştur. Hesaplamalı çalışmalar, C5 bileşiğinin moleküler yerleştirmede en yüksek bağlanma enerjisine (-9,9 kcal/mol) sahip olduğunu göstermiştir. Potansiyel antidiyabetik özelliklere sahip olduğu tespit edilen kurkumin bileşikleri, moleküler yerleştirme analizine göre 3A4A reseptörüne karşı referans bileşik akarboza göre daha yüksek bağlanma enerjisi göstermiştir. Kurkumin türevi bileşiklerin antidiyabetik etkileri, gelecekteki ilaç adayı moleküller için umut vericidir.

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Cite This Article

Köprü, S. (2026). Quantum Chemical Calculation And Molecular Docking Studies Of Coumarin Based Curcumins As α-Glucosidase Inhibitors. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi, Cilt: 13 Sayı: 1, 165–178. https://doi.org/10.35193/bseufbd.1838955

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References (41)

  1. Moradi Baniasadi, M., Arzhang, P., Setayesh, A., Moradi, M., Nasli-Esfahani, E., & Azadbakht, L. (2025). The effect of turmeric/curcumin supplementation on anthropometric indices in subjects with prediabetes and type 2 diabetes mellitus: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Nutrition & Diabetes, 15(1), 34.
  2. Kurşun Aktar, B. S., Sıcak, Y., Bakırdöven, A., Tatar Yılmaz, G., Kaya, S., Karaküçük-İyidoğan, A., & Oruç-Emre, E. E. (2025). Novel Pyrrolidine-Based Pyrazolines as α-Glucosidase Inhibitors: Microwave-Assisted Synthesis, Antidiabetic Activity, In Silico ADMET Prediction, Molecular Docking, and Molecular Dynamics Simulations. ACS omega. https://doi.org/10.1021/acsomega.5c05455
  3. Magliano, D. J.; Boyko, E. J. IDF Diabetes Atlas 11th Edition 2025, Scientific Committee; International Diabetes Federation, 2025. https://doi.org/10.1093/ndt/gfaf177
  4. Shibib, L.; Al-Qaisi, M.; Guess, N.; Miras, A. D.; Greenwald, S.E.; Pelling, M.; Ahmed, A. Manipulation of post-prandial hyperglycaemia in type 2 diabetes: an update for practitioners. Diabetes, Metab. Syndr. Obes. 2024, 17, 3111−3130. https://doi.org/10.2147/DMSO.S458894
  5. Imran, S.; Taha, M.; Ismail, N. H.; Kashif, S. M.; Rahim, F.;Jamil, W.; Wahab, H.; Khan, K. M. Synthesis, in vitro and docking studies of new flavone ethers as α-glucosidase inhibitors. Chemical Biology & Drug Design 2016, 87 (3), 361−373. https://doi.org/10.1111/cbdd.12666
  6. Santos, C. M.; Proença, C.; Freitas, M.; Araújo, A. N.; Silva, A. M.; Fernandes, E. Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones. Food &Function 2022, 13 (14), 7930−7941. https://doi.org/10.1039/D2FO00023G
  7. Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., & Supuran, C. T. (2021). Natural products in drug discovery: advances and opportunities. Nature reviews Drug discovery, 20(3), 200-216. https://doi.org/10.1038/s41573-020-00114-z
  8. Maurya, A. K., & Mishra, N. (2022). Coumarin-based combined computational study to design novel drugs against Candida albicans. Journal of Microbiology, 60(12), 1201-1207. https://doi.org/10.1007/s12275-022-2279-5.
  9. Flores-Morales, V., Villasana-Ruíz, A. P., Garza-Veloz, I., González-Delgado, S., & Martinez-Fierro, M. L. (2023). Therapeutic effects of coumarins with different substitution patterns. Molecules, 28(5), 2413. https://doi.org/10.3390/molecules28052413
  10. Sohn, S. I., Priya, A., Balasubramaniam, B., Muthuramalingam, P., Sivasankar, C., Selvaraj, A.,. & Pandian, S. (2021). Biomedical applications and bioavailability of curcumin: An updated overview. Pharmaceutics, 13(12), 2102. https://doi.org/10.3390/pharmaceutics13122102
  11. Anthwal, A., Singh, K., Rawat, M. S. M., Tyagi, A. K., Aggarwal, B. B., & Rawat, D. S. (2014). C5-curcuminoid-dithiocarbamate based molecular hybrids: Synthesis and anti-inflammatory and anti-cancer activity evaluation. RSC Advances, 4(54), 28756-28764. https://doi.org/10.1039/C4RA03655G
  12. Singh, A., Singh, J. V., Rana, A., Bhagat, K., Gulati, H. K., Kumar, R.,. & Bedi, P. M. S. (2019). Monocarbonyl curcumin-based molecular hybrids as potent antibacterial agents. ACS omega, 4(7), 11673-11684. https://doi.org/10.1021/acsomega.9b01109
  13. Abrahams, S., Haylett, W. L., Johnson, G., Carr, J. A., & Bardien, S. (2019). Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review. Neuroscience, 406, 1-21. https://doi.org/10.1016/j.neuroscience.2019.02.020
  14. Gholipour, F., Amini, M., Baradaran, B., Mokhtarzadeh, A., & Eskandani, M. (2023). Anticancer properties of curcumin-treated Lactobacillus plantarum against the HT-29 colorectal adenocarcinoma cells. Scientific Reports, 13(1), 2860. https://doi.org/10.1038/s41598-023-29462-7
  15. Hamaguchi, T., Ono, K., & Yamada, M. (2010). Curcumin and Alzheimer's disease. CNS neuroscience & therapeutics, 16(5), 285-297. https://doi.org/10.1111/j.1755-5949.2010.00147.x
  16. Mishra, S., Karmodiya, K., Surolia, N., & Surolia, A. (2008). Synthesis and exploration of novel curcumin analogues as anti-malarial agents. Bioorganic & medicinal chemistry, 16(6), 2894-2902. https://doi.org/10.1016/j.bmc.2007.12.054
  17. Khaldi-Khellafi, N., Makhloufi-Chebli, M., Oukacha-Hikem, D., Bouaziz, S. T., Lamara, K. O., Idir, T.,. & Dumas, F. (2019). Green synthesis, antioxidant and antibacterial activities of 4-aryl-3, 4-dihydropyrimidinones/thiones derivatives of curcumin. Theoretical calculations and mechanism study. Journal of Molecular Structure, 1181, 261-269. https://doi.org/10.1016/j.molstruc.2018.12.104
  18. Zhang, Y., Liang, D., Dong, L., Ge, X., Xu, F., Chen, W.,. & Liang, G. (2015). Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury. Respiratory research, 16(1), 43. https://doi.org/10.1186/s12931-015-0199-1
  19. Jalilian, F., Moradi, S., Hosseinzadeh, L., Zarei, A., Raeisi, P., Shahlaei, M.,. & Adibi, H. (2025). Synthesis, characterization, cytotoxic investigation of curcumin-based 4-phenylchromene derivatives, and study of DNA interaction using experimental and computational methods. Journal of Molecular Liquids, 424, 127063. https://doi.org/10.1016/j.molliq.2025.127063
  20. Amalraj, A., Pius, A., Gopi, S., & Gopi, S. (2017). Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives–A review. Journal of traditional and complementary medicine, 7(2), 205-233. https://doi.org/10.1016/j.jtcme.2016.05.005
  21. Afrdi, M. B., Sardar, H., Serdaroğlu, G., Shah, S. W. A., Alsharif, K. F., & Khan, H. (2024). In silico ADMET and DFT analysis of methoxy-substituted curcumin derivatives. Inorganic Chemistry Communications, 168, 112943. https://doi.org/10.1016/j.inoche.2024.112943
  22. Khudhayer Oglah, M., & Fakri Mustafa, Y. (2020). Curcumin analogs: synthesis and biological activities. Medicinal Chemistry Research, 29(3), 479-486. https://doi.org/10.1007/s00044-019-02497-0
  23. Dennington, R. D. I. I., Keith, T. A., & Millam, J. M. (2016). GaussView 6.0. 16. Semichem Inc.: Shawnee Mission, KS, USA, 143-150. https://gaussian.com/gaussview6/
  24. Frisch, M. J., Trucks G.W., et al. Gaussian 09, Revision D.01 Gaussian, Inc, Wallingford, CT (2009). http://www. gaussian. com/.
  25. Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of small molecules. Scientific reports, 7(1), 42717. https://doi.org/10.1038/srep42717
  26. Vicidomini, C., Fontanella, F., D’Alessandro, T., & Roviello, G. N. (2024). A survey on computational methods in drug discovery for neurodegenerative diseases. Biomolecules, 14(10), 1330.
  27. Prieto-Martínez, F. D., López-López, E., Juárez-Mercado, K. E., & Medina-Franco, J. L. (2019). Computational drug design methods—current and future perspectives. In silico drug design, 19-44. https://doi.org/10.1016/B978-0-12-816125
  28. Prabhu, C., Rajesh, P., Lawrence, M., Sahaya Jude Dhas, S., & Almansour, A. I. (2025). Computational aspects of DFT, HOMO-LUMO, PED, molecular docking, and basic characterisations of Octadec-9-Enoic Acid (C18H34O2). Molecular Physics, 123(4), e2385572. https://doi.org/10.1080/00268976.2024.2385572
  29. Tasli, P. T., Soganci, T., Kart, S. O., Kart, H. H., & Ak, M. (2021). Quantum mechanical calculations of different monomeric structures with the same electroactive group to clarify the relationship between structure and ultimate optical and electrochemical properties of their conjugated polymers. Journal of Physics and Chemistry of Solids, 149, 109720. https://doi.org/10.1016/j.jpcs.2020.109720
  30. Akbari, Z., Stagno, C., Iraci, N., Efferth, T., Omer, E. A., Piperno, A.,. & Micale, N. (2024). Biological evaluation, DFT, MEP, HOMO-LUMO analysis, and ensemble docking studies of Zn (II) complexes of bidentate, and tetradentate Schiff base ligands as antileukemia agents. Journal of Molecular Structure, 1301, 137400. https://doi.org/10.1016/j.molstruc.2023.137400
  31. Jayaprakash, P., Caroline, M. L., Sudha, S., Ravisankar, R., Vinitha, G., Ramesh, P., & Raju, E. (2020). Synthesis, growth, optical and third-order nonlinear optical properties of l-Phenylalanine d-Mandelic acid single crystal for photonic device applications. Journal of Materials Science: Materials in Electronics, 31(22), 20460-20471. https://doi.org/10.1007/s10854-020-04565-3
  32. Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced drug delivery reviews, 64, 4-17. https://doi.org/10.1016/j.addr.2012.09.019
  33. Basaran, E., Kopru, S., Akkoc, S., & Turkmenoglu, B. (2024). Investigation of newly synthesized fluorinated isatin-hydrazones by in vitro antiproliferative activity, molecular docking, adme analysis, and e-pharmacophore modeling. ACS omega, 9(24), 26503-26518. https://pubs.acs.org/doi/10.1021/acsomega.4c03014.
  34. Ballabh, P., Braun, A., & Nedergaard, M. (2004). The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiology of disease, 16(1), 1-13. https://doi.org/10.1016/j.nbd.2003.12.016
  35. Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2018). Blood-brain barrier: from physiology to disease and back. Physiological reviews. https://doi.org/10.1152/physrev.00050.2017
  36. Sohn, S. I., Priya, A., Balasubramaniam, B., Muthuramalingam, P., Sivasankar, C., Selvaraj, A.,. & Pandian, S. (2021). Biomedical applications and bioavailability of curcumin: An updated overview. Pharmaceutics, 13(12), 2102. https://doi.org/10.3390/pharmaceutics13122102
  37. Singh, A., Singh, J. V., Rana, A., Bhagat, K., Gulati, H. K., Kumar, R.,. & Bedi, P. M. S. (2019). Monocarbonyl curcumin-based molecular hybrids as potent antibacterial agents. ACS omega, 4(7), 11673-11684. https://doi.org/10.1021/acsomega.9b01109
  38. Khaldi-Khellafi, N., Makhloufi-Chebli, M., Oukacha-Hikem, D., Bouaziz, S. T., Lamara, K. O., Idir, T.,. & Dumas, F. (2019). Green synthesis, antioxidant and antibacterial activities of 4-aryl-3, 4-dihydropyrimidinones/thiones derivatives of curcumin. Theoretical calculations and mechanism study. Journal of Molecular Structure, 1181, 261-269. https://doi.org/10.1016/j.molstruc.2018.12.104
  39. Zhang, Y., Liang, D., Dong, L., Ge, X., Xu, F., Chen, W.,. & Liang, G. (2015). Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury. Respiratory research, 16(1), 43. https://doi.org/10.1186/s12931-015-0199-1
  40. Jalilian, F., Moradi, S., Hosseinzadeh, L., Zarei, A., Raeisi, P., Shahlaei, M.,. & Adibi, H. (2025). Synthesis, characterization, cytotoxic investigation of curcumin-based 4-phenylchromene derivatives, and study of DNA interaction using experimental and computational methods. Journal of Molecular Liquids, 424, 127063. https://doi.org/10.1016/j.molliq.2025.127063
  41. Akbari, Z., Stagno, C., Iraci, N., Efferth, T., Omer, E. A., Piperno, A.,. & Micale, N. (2024). Biological evaluation, DFT, MEP, HOMO-LUMO analysis, and ensemble docking studies of Zn (II) complexes of bidentate, and tetradentate Schiff base ligands as antileukemia agents. Journal of Molecular Structure, 1301, 137400. https://doi.org/10.1016/j.molstruc.2023.137400