DOI: https://doi.org/10.14710/jksa.27.7.316-327

QSAR, Molecular Docking, and Molecular Dynamic of Novel Coumarin Derivatives as α-Glucosidase Inhibitor

1Department of Chemistry, Faculty of Science and Technology, Universitas Islam Negeri Walisongo, Semarang, 50181, Indonesia

2Al Irsyad Al Islamiyyah Boarding School Purwokerto, Banyumas 53113, Indonesia

3School of Chemistry, Faculty of Science, The University of Sydney, Camperdown NSW 2050, Australia

Received: 18 Jan 2024; Revised: 13 Jun 2024; Accepted: 19 Jun 2024; Published: 31 Jul 2024.
Open Access Copyright 2024 Jurnal Kimia Sains dan Aplikasi under http://creativecommons.org/licenses/by-sa/4.0.

Citation Format:
Cover Image
Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder posing a significant health risk. Effective treatments are continually sought. Coumarin derivatives with oxime ester groups have shown potential as antidiabetic agents by inhibiting the α-glucosidase enzyme, a key player in glycoprotein metabolism and postprandial hyperglycemia control. This makes lysosomal α-glucosidase a promising therapeutic target. A study used 28 coumarin derivatives with known α-glucosidase inhibitory IC50 values for computer-assisted drug design (CADD) through quantitative structure-activity relationship (QSAR) analysis, yielding a statistically robust equation for guiding new compound development. Subsequently, eleven new coumarin derivatives with oxime ester groups were synthesized, showing enhanced α-glucosidase inhibitory activity compared to the initial set. Molecular docking assays indicated that compounds 32, 37, 38, and 39 had lower free energy values than the native ligand, suggesting higher stability in target protein interactions. Notably, compound 38 had the lowest free energy (-8.351) and demonstrated lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) than the original ligand, indicating greater stability. The QSAR equation derived is:

Log IC50 = 2.886 - 0.054 (LUMO) + 0.073 (μ) – 0.148 (α) – 0.046 (RD) + 0.046 (BM) + 0.001 (Vvdw) – 0.421 (qC2) + 1.138 (qC8) – 0.092 (qC9) + 2.61 (qC10) + 1.354 (qN1) (Eq 1) n=28; R=0.918; R2=0.843; SD=0.196; F hit/F tab=3.169; Sig =<0.01; PRESS = 1.376.

Compound 38’s SMILES notation is:

C\C(=N/OC(=O)\C=C/C1=CC=C(Br)C=C1)C1=CC2=CC(O)=C(CC(O)=O)C=C2OC1=O).

Fulltext View|Download
Keywords: Alpha-glucosidase inhibitor; Coumarin; Molecular dynamic; Molecular docking; QSAR
Funding: BOPTN UIN Walisongo Semarang under contract 980/Un.10.0/R/HK.01.14/4/2023

Article Metrics:

Article Info
Section: Research Articles
Language : EN
Recent articles
Virtual Screening of Syzygium cumini (L.) Skeels Flavonoid Compounds as SARS-CoV-2 Main Protease Therapy Candidates A Cycloartane Triterpenoid and Steroid from The Leaves of Aglaia shawiana Merr. (Meliaceae) Synthesis and Antibacterial Activity Test of Dibutyl Tin (IV) N-Ethylbenzyl Dithiocarbamate Compound Against Salmonella Thy.Atcc.14028 and Propionibacterium acnes Bacteria Synthesis and Characterization Membrane Nanofibers Cellulose Acetate-Zeolite for Metal Pb (II) Adsorption More recent articles
Most cited articles
Profil Kandungan Protein dan Tekstur Tahu Akibat Penambahan Fitat pada Proses Pembuatan Tahu Sintesis Silika Kristalin Menggunakan Surfaktan Cetiltrimetilamonium Bromida (CTAB) dan Trimetilamonium Klorida (TMACl) sebagai Pencetak Pori Pirolisis Kulit Biji Jambu Mete (Anacardium occidentale L.) dengan Katalis Ni-Ag/Zeolit Pengaruh Waktu pada Pembentukan Kalsium Fosfat dengan Sistem Membran Selulosa Bakterial Antioxidant Activity of Daemonorops draco Resin More cited articles
  1. Muhammad Rizqi Fahriza, Faktor Mempengaruhi yang Penyebab Kejadian Diabetes Mellitus (DM), OSF Preprints, (2019), https://doi.org/10.31219/osf.io/v82ea
  2. Chinmay D. Deshmukh, Anurekha Jain, B. Nahata, Diabetes Mellitus: A Review, International Journal of Pure & Applied Bioscience, 3, 3, (2015), 224-230
  3. Md Saidur Rahman, Khandkar Shaharina Hossain, Sharnali Das, Sushmita Kundu, Elikanah Olusayo Adegoke, Md. Ataur Rahman, Md. Abdul Hannan, Md Jamal Uddin, Myung-Geol Pang, Role of Insulin in Health and Disease: An Update, International Journal of Molecular Sciences, 22, 12, (2021), 6403 https://doi.org/10.3390/ijms22126403
  4. Pia V. Röder, Bingbing Wu, Yixian Liu, Weiping Han, Pancreatic regulation of glucose homeostasis, Experimental & Molecular Medicine, 48, 3, (2016), e219-e219 https://doi.org/10.1038/emm.2016.6
  5. Hanbing Li, Yuanfa Yao, Linghuan Li, Coumarins as potential antidiabetic agents, Journal of Pharmacy and Pharmacology, 69, 10, (2017), 1253-1264 https://doi.org/10.1111/jphp.12774
  6. Sara Ranđelović, Robbert Bipat, A Review of Coumarins and Coumarin-Related Compounds for Their Potential Antidiabetic Effect, Clinical Medicine Insights: Endocrinology and Diabetes, 14, (2021), https://doi.org/10.1177/11795514211042023
  7. Yinbo Pan, Teng Liu, Xiaojing Wang, Jie Sun, Research progress of coumarins and their derivatives in the treatment of diabetes, Journal of Enzyme Inhibition and Medicinal Chemistry, 37, 1, (2022), 616-628 https://doi.org/10.1080/14756366.2021.2024526
  8. Shashank M. Patil, Reshma Mary Martiz, A. M. Satish, Abdullah M. Shbeer, Mohammed Ageel, Mohammed Al-Ghorbani, Lakshmi Ranganatha, Saravanan Parameswaran, Ramith Ramu, Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches, Molecules, 27, 12, (2022), 3888 https://doi.org/10.3390/molecules27123888
  9. Paul M. Dewick, The Mevalonate and Deoxyxylulose Phosphate Pathways: Terpenoids and Steroids, in: Medicinal Natural Products: A Biosynthetic Approach, John Wiley & Sons, 2001, https://doi.org/10.1002/0470846275.ch5
  10. Vladimir K. Mukhomorov, Biological activity of chemical compounds and their molecular Structure-information approach, Journal of Chemical Engineering and Chemistry Research, 1, 1, (2014), 54-65
  11. Włodzimierz Lewandowski, Hanna Lewandowska, Aleksandra Golonko, Grzegorz Świderski, Renata Świsłocka, Monika Kalinowska, Correlations between molecular structure and biological activity in "logical series" of dietary chromone derivatives, PLoS ONE, 15, 8, (2020), e0229477 https://doi.org/10.1371/journal.pone.0229477
  12. Hugo Hernandez, Livy Shivraj, In Silico Toxicity Prediction Using an Integrative Multimodel Approach, ForsChem Research Reports, 5, (2020),
  13. Samuel Genheden, Anna Reymer, Patricia Saenz-Méndez, Leif A. Eriksson, Computational Chemistry and Molecular Modelling Basics, in: S. Martín-Santamaría (Ed.) Computational Tools for Chemical Biology, The Royal Society of Chemistry, 2017, https://doi.org/10.1039/9781788010139-00001
  14. Xin Zhang, Ying-Ying Zheng, Chun-Mei Hu, Xiao-Zheng Wu, Jing Lin, Zhuang Xiong, Kun Zhang, Xue-Tao Xu, Synthesis and biological evaluation of coumarin derivatives containing oxime ester as α-glucosidase inhibitors, Arabian Journal of Chemistry, 15, 9, (2022), 104072 https://doi.org/10.1016/j.arabjc.2022.104072
  15. Anjar Purba Asmara, Mudasir Mudasir, Dwi Siswanta, Analisis Hubungan Kuantitatif Struktur dan Aktivitas Senyawa Turunan Triazolopiperazin Amida Menggunakan Metode Semiempirik AM1, Elkawnie: Journal of Islamic Science Technology, 1, 2, (2015), 125-138
  16. Anjar Purba Asmara, Mudasir Mudasir, Dwi Siswanta, Studi Qsar Senyawa Turunan Triazolopiperazin Amida Sebagai Inhibitor Enzim Dipeptidil Peptidase-IV (DPP IV) Menggunakan Metode Semiempirik AM1, BIMIPA, 23, 3, (2013), 288-296
  17. Ruslin Hadanu, Salim Idris, I Wayan Sutapa, QSAR Analysis of Benzothiazole Derivatives of Antimalarial Compounds Based on AM1 Semi-Empirical Method, Indonesian Journal of Chemistry, 15, 1, (2015), 86-92 https://doi.org/10.22146/ijc.21228
  18. Mutista Hafshah, Lilis Karlina, Desain Turunan Kalkon Baru Sebagai Antikanker Payudara Berdasarkan Molecular Docking, Walisongo Journal of Chemistry, 2, 2, (2019), 57-63 https://doi.org/10.21580/wjc.v2i2.6025
  19. Mudasir Mudasir, Iqmal Tahir, Ida Puji Astuti Maryono Putri, Quantitative Structure and Activity Relationship Analysis of 1, 2, 4-Thiadiazoline Fungicides Based on Molecular Structure Calculated by Am1 Method, Indonesian Journal of Chemistry, 3, 1, (2003), 39-47
  20. Mustofa Mustofa, Iqmal Tahir, Jumina Jumina, QSAR study of 1, 10-phenanthroline derivatives as the antimalarial compounds using electronic descriptors based on semiempirical AM1 calculation, Indonesian Journal of Chemistry, 2, 2, (2010), 91-96
  21. Khusna Arif Rakhman, Nur Asbirayani Limatahu, Hasbul Budiman Karim, Muhammad Ikhlas Abdjan, Kajian Senyawa Turunan Benzopirazin sebagai Antimalaria Menggunakan Metode HKSA dan MLR, EduChemia, 4, 2, (2019), 112-126 https://dx.doi.org/10.30870/educhemia.v4i2.4989
  22. T. Thalheim, D. Wondrousch, S. Stöckl, D. Mulliner, R. U. Ebert, R. Kühne, G. Schüürmann, Diagnostic of tautomer behaviour on QSAR models and AM1 optimisation, Journal of Cheminformatics, 3, (2011), P24 https://doi.org/10.1186/1758-2946-3-S1-P24
  23. Mutista Hafshah, Irvan Maulana Firdaus, Suratno Suratno, Quantitative Relationships Between Structure and Activity of Gamma-Carboline Derivative Compounds as Anti-Bovine Viral Diarrhea Virus (BVDV) Using Semi-Empirical AM1 Method, Walisongo Journal of Chemistry, 5, 2, (2022), 182-193 https://doi.org/10.21580/wjc.v5i2.13409
  24. Ponco Iswanto, Isnaeni Tatik Rosdiyana, Iqmal Tahir, Hubungan kuantitatif struktur dan aktivitas antikanker senyawa turunan estradiol hasil perhitungan metode semiempiris PM3, BIMIPA, 17, 1, (2007), 12-20
  25. Akhilesh Kumar Maurya, Viswajit Mulpuru, Nidhi Mishra, Discovery of Novel Coumarin Analogs against the α-Glucosidase Protein Target of Diabetes Mellitus: Pharmacophore-Based QSAR, Docking, and Molecular Dynamics Simulation Studies, ACS Omega, 5, 50, (2020), 32234-32249 https://doi.org/10.1021/acsomega.0c03871
  26. Thi-Hong-Truc Phan, Kowit Hengphasatporn, Yasuteru Shigeta, Wanting Xie, Phornphimon Maitarad, Thanyada Rungrotmongkol, Warinthorn Chavasiri, Designing Potent α-Glucosidase Inhibitors: A Synthesis and QSAR Modeling Approach for Biscoumarin Derivatives, ACS Omega, 8, 29, (2023), 26340-26350 https://doi.org/10.1021/acsomega.3c02868
  27. Muhammad Sulaiman Zubair, Saipul Maulana, Alwiyah Mukaddas, Penambatan molekuler dan simulasi dinamika molekuler senyawa dari genus nigella terhadap penghambatan aktivitas enzim protease HIV-1, Jurnal Farmasi Galenika, 6, 1, (2020), 132-140 https://doi.org/10.22487/j24428744.2020.v6.i1.14982
  28. Ming-Hui Li, Quan Luo, Xiang-Gui Xue, Ze-Sheng Li, Molecular dynamics studies of the 3D structure and planar ligand binding of a quadruplex dimer, Journal of Molecular Modeling, 17, 3, (2011), 515-526 https://doi.org/10.1007/s00894-010-0746-0
  29. Ranjan K. Mohapatra, Kuldeep Dhama, Amr Ahmed El–Arabey, Ashish K. Sarangi, Ruchi Tiwari, Talha Bin Emran, Mohammad Azam, Saud I. Al-Resayes, Mukesh K. Raval, Veronique Seidel, Mohnad Abdalla, Repurposing benzimidazole and benzothiazole derivatives as potential inhibitors of SARS-CoV-2: DFT, QSAR, molecular docking, molecular dynamics simulation, and in-silico pharmacokinetic and toxicity studies, Journal of King Saud University - Science, 33, 8, (2021), 101637 https://doi.org/10.1016/j.jksus.2021.101637
  30. Emmanuel Israel Edache, Adamu Uzairu, Paul Andrew Mamza, Gideon Adamu Shallangwa, Structure-based simulated scanning of rheumatoid arthritis inhibitors: 2D-QSAR, 3D-QSAR, docking, molecular dynamics simulation, and lipophilicity indices calculation, Scientific African, 15, (2022), e01088 https://doi.org/10.1016/j.sciaf.2021.e01088
  31. Lalu Sanik Wahyu Fadil Amrulloh, Nuraini Harmastuti, Andri Prasetiyo, Rina Herowati, Analysis of Molecular Docking and Dynamics Simulation of Mahogany (Swietenia macrophylla King) Compounds Against the PLpro Enzyme SARS-COV-2, Jurnal Farmasi dan Ilmu Kefarmasian Indonesia, 10, 3, (2023), 347-359 https://doi.org/10.20473/jfiki.v10i32023.347-359
  32. Devendra K. Dhaked, Jitender Verma, Anil Saran, Evans C. Coutinho, Exploring the binding of HIV-1 integrase inhibitors by comparative residue interaction analysis (CoRIA), Journal of Molecular Modeling, 15, 3, (2009), 233-245 https://doi.org/10.1007/s00894-008-0399-4
  33. Ponco Iswanto, Eva Vaulina Yulistia Delsy, Ely Setiawan, Fiandy Aminullah Putra, Quantitative Structure-Property Relationship Analysis Against Critical Micelle Concentration of Sulfonate-Based Surfactant Based on Semiempirical Zindo/1 Calculation, Molekul, 14, 2, (2019), 78-83 https://doi.org/10.20884/1.jm.2019.14.2.467
  34. Ponco Iswanto, Irvan Maulana Firdaus, Ahmad Fawwaz Dafaulhaq, Ahmad Ghifari Ramadhani, Maylani Permata Saputri, Heny Ekowati, Quantitative Structure-Activity Relationship of 3-Thiocyanate-1H-Indoles Derived Compounds as Antileukemia by AM1, PM3, and RM1 Methods, Jurnal Kimia Sains dan Aplikasi, 26, 3, (2023), 109-117 https://doi.org/10.14710/jksa.26.3.109-117
  35. Eva Vaulina, Ponco Iswanto, Model QSAR Senyawa Fluorokuinolon Baru Sebagai Zat Antibakteri Salmonella Thypimurium, Molekul, 1, 1, (2006), 10-18 http://dx.doi.org/10.20884/1.jm.2006.1.1.17
  36. Purnawan Pontana Putra, Teori dan Tutorial Molecular Docking Menggunakan AutoDock Vina, Wawasan Ilmu, Banyumas, 2022,
  37. Chan Kyung Kim, Soo Gyeong Cho, Chang Kon Kim, Mi-Ri Kim, Hai Whang Lee, Prediction of Physicochemical Properties of Organic Molecules Using Semi-Empirical Methods, Bulletin of the Korean Chemical Society, 34, 4, (2013), 1043-1046 https://doi.org/10.5012/bkcs.2013.34.4.1043
  38. Muneerah Mogren Al Mogren, Enfale Zerroug, Salah Belaidi, Ahlam BenAmor, Sarah Dhaif Allah Al Harbi, Molecular structure, drug likeness and QSAR modeling of 1,2-diazole derivatives as inhibitors of enoyl-acyl carrier protein reductase, Journal of King Saud University - Science, 32, 4, (2020), 2301-2310 https://doi.org/10.1016/j.jksus.2020.03.007
  39. Samia Boudergua, Salah Belaidi, Muneerah Mogren AlMogren, Aouda Bounif, Mohamed Bakhouch, Samir Chtita, QSAR modeling using the Gaussian process applied for a series of flavonoids as potential antioxidants, Journal of King Saud University - Science, 35, 8, (2023), 102898 https://doi.org/10.1016/j.jksus.2023.102898
  40. Daratu Eviana Kusuma Putri, Harno Dwi Pranowo, Anugrah Ricky Wijaya, Novia Suryani, Maisari Utami, Artania Adnin Tri Suma, Woo Jin Chung, Saeedah Musaed Almutairi, Dina S. Hussein, Rabab Ahmed Rasheed, Venkatalakshmi Ranganathan, The predicted models of anti-colon cancer and anti-hepatoma activities of substituted 4-anilino coumarin derivatives using quantitative structure-activity relationship (QSAR), Journal of King Saud University - Science, 34, 3, (2022), 101837 https://doi.org/10.1016/j.jksus.2022.101837
  41. Giuseppe Floresta, Agostino Cilibrizzi, Vincenzo Abbate, Ambra Spampinato, Chiara Zagni, Antonio Rescifina, FABP4 inhibitors 3D-QSAR model and isosteric replacement of BMS309403 datasets, Data in Brief, 22, (2019), 471-483 https://doi.org/10.1016/j.dib.2018.12.047
  42. Natalia Piekuś-Słomka, Mariusz Zapadka, Bogumiła Kupcewicz, Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors, Arabian Journal of Chemistry, 15, 11, (2022), 104204 https://doi.org/10.1016/j.arabjc.2022.104204
  43. Alicia Rosell-Hidalgo, Anthony L. Moore, Taravat Ghafourian, Prediction of drug-induced mitochondrial dysfunction using succinate-cytochrome c reductase activity, QSAR and molecular docking, Toxicology, 485, (2023), 153412 https://doi.org/10.1016/j.tox.2022.153412
  44. Emmy Yuanita, Sudirman, Ni Komang Tri Dharmayani, Maria Ulfa, Jufrizal Syahri, Quantitative structure–activity relationship (QSAR) and molecular docking of xanthone derivatives as anti-tuberculosis agents, Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 21, (2020), 100203 https://doi.org/10.1016/j.jctube.2020.100203
  45. M. Yusuf, N. Dari, E. Utama, PM3 Semi-Empirical Method on the Ring Opening Polymerization of ε-Caprolactone Using Bis (Benzoyltrifluoroacetone)Zirconium(IV) Chloride as catalyst, Journal of Physics: Conference Series, 1462, (2020), 012054 https://doi.org/10.1088/1742-6596/1462/1/012054
  46. Gordon Lemmon, Jens Meiler, Towards Ligand Docking Including Explicit Interface Water Molecules, PLoS ONE, 8, 6, (2013), e67536 https://doi.org/10.1371/journal.pone.0067536
  47. Shailima Rampogu, Gihwan Lee, Jun Sung Park, Keun Woo Lee, Myeong Ok Kim, Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2, International Journal of Molecular Sciences, 23, 3, (2022), 1771 https://doi.org/10.3390/ijms23031771

Last update:

No citation recorded.

Last update: 2024-11-22 07:48:01

No citation recorded.