Palavras-chave
antioxidante
inibição da α-amilase
arborside-C
arborside-D
Como Citar
Resumo
Descobriu-se que os metabólitos secundários das plantas medicinais possuem um amplo espectro de propriedades terapêuticas. Este estudo investiga a extração sequencial, os fitoquímicos quantitativos e as avaliações de bioatividade da folha de Nyctanthes arbor-tristis cultivada no Nepal. O extrato metanólico contém os fenólicos mais altos e resultou nos menores valores de IC50 de 56±3 µg/mL e 157±3 µg/mL, em ensaios de inibição de antioxidante e α-amilase, respectivamente. Descobriu-se que o extrato de hexano contém flavonoides abundantes e é o mais letal para o camarão napuili com LC50 de 87±5 µg/mL. Os fitoquímicos arborside-C (ASC) e arborside-D (ASD) foram considerados os ligantes mais potentes para se ligarem à α-amilase (PDB ID: 4GQR), como resultado da simulação de acoplamento e dinâmica molecular. As alterações de energia livre calculadas pelo método MMPBSA e o perfil ADMET dos candidatos a sucesso foram apoiados pela espontaneidade das reações de formação de complexos e sua eficácia farmacocinética, respectivamente. Este estudo propõe dois compostos como candidatos a sucesso para o alvo da α-amilase. Recomenda-se ainda a caracterização biológica usando uma abordagem in vivo para avaliar sua validação farmacológica precisa.
Referências
Abraham, M. J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J. C.; Hess, B.; Lindah, E. Gromacs: High Performance Molecular Simulations through Multi-Level Parallelism from Laptops to Supercomputers. SoftwareX. 2015, 1 (2), 19–25. https://doi.org/10.1016/j.softx.2015.06.001
Adcock, S. A.; McCammon, J. A. Molecular Dynamics: Survey of Methods for Simulating the Activity of Proteins. Chem. Rev. 2006, 106, 1589–1615. https://doi.org/10.1021/cr040426m
Agrawal, J.; Pal, A. Nyctanthes arbor-tristis Linn - A Critical Ethnopharmacological Review. J. Ethnopharmacol. 2013, 146, 645–658. https://doi.org/10.1016/j.jep.2013.01.024
Ahmed, S.; Ali, M. C.; Ruma, R. A.; Mahmud, S.; Paul, G. K.; Saleh, M. A.; Alshahrani, M. M.; Obaidullah, A. J.; Biswas, S. K.; Rahman, M. M.; Rahman, M. M.; Islam, M. R. Molecular Docking and Dynamics Simulation of Natural Compounds from Betel Leaves (Piper Betle L.) for Investigating the Potential Inhibition of Alpha-Amylase and Alpha-Glucosidase of Type 2 Diabetes. Molecules. 2022, 27 (14), 4526. https://doi.org/10.3390/molecules27144526
Aier, I.; Varadwaj, P. K.; Raj, U. Structural Insights into Conformational Stability of Both Wild-Type and Mutant EZH2 Receptor. Sci. Rep. 2016, 6 (1), 34984. https://doi.org/10.1038/srep34984
Akki, K. S.; Krishnamurthy, G.; Bhoja Naik, H. S. Phytochemical Investigations and in vitro Evaluation of Nyctanthes arbor-tristis Leaf Extracts for Antioxidant Property. J. Pharm. Res. 2009, 2 (4), 752–755.
Banerjee, P.; Eckert, A. O.; Schrey, A. K.; Preissner, R. ProTox-II: A Webserver for the Prediction of Toxicity of Chemicals. Nucleic Acids Res. 2018, 46 (1), 257–263. https://doi.org/10.1093/nar/gky318
Banu, K. S.; Cathrine, L. General Techniques Involved in Phytochemical Analysis. Int. J. Adv. Res. Chem. Sci. 2015, 2 (4), 25–32.
Basnet, S.; Ghimire, M. P.; Lamichhane, T. R.; Adhikari, R.; Adhikari, A. Identification of Potential Human Pancreatic Αamylase Inhibitors from Natural Products by Molecular Docking, MM/GBSA Calculations, MD Simulations, and ADMET Analysis. PLoS One. 2023, 18, 1–13. https://doi.org/10.1371/journal.pone.0275765
Bb, C.; Pandeya, S.; Kp, G.; Bharati L Phytochemical Screening and Cytotoxic Activity of Nyctanthes arbor tristis. Indian Res. J. Pharm. Sci. 2015, 2 (2), 205–217.
Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank. Nucleic Acids Res. 2000, 28 (1), 235-242. https://doi.org/10.1093/nar/28.1.235
Bitew, M.; Desalegn, T.; Demissie, T. B.; Belayneh, A.; Endale, M.; Eswaramoorthy, R. Pharmacokinetics and Drug-Likeness of Antidiabetic Flavonoids: Molecular Docking and DFT Study. PLoS One. 2021, 16, 0260853. https://doi.org/10.1371/journal.pone.0260853
Blois, M. S. Antioxidant Determinations by the Use of a Stable Free Radical. Nature. 1958, 181 (4617), 1199–1200. https://doi.org/10.1038/1811199a0
Butler, M. S. The Role of Natural Product Chemistry in Drug Discovery. J. Nat. Prod. 2004, 67, 2141–2153. https://doi.org/10.1021/np040106y
Carpenter, T. S.; Kirshner, D. A.; Lau, E. Y.; Wong, S. E.; Nilmeier, J. P.; Lightstone, F. C. A Method to Predict Blood-Brain Barrier Permeability of Drug-Like Compounds Using Molecular Dynamics Simulations. Biophys J. 2014, 107 (3), 630–641. https://doi.org/10.1016/j.bpj.2014.06.024
Cele, N.; Awolade, P.; Seboletswe, P.; Olofinsan, K.; Islam, M. S.; Singh, P. α-Glucosidase and α-Amylase Inhibitory Potentials of Quinoline–1,3,4-Oxadiazole Conjugates Bearing 1,2,3-Triazole with Antioxidant Activity, Kinetic Studies, and Computational Validation. Pharmaceuticals. 2022, 15 (8), 1035. https://doi.org/10.3390/ph15081035
Chandra, S.; Khan, S.; Avula, B.; Lata, H.; Yang, M. H.; Elsohly, M. A.; Khan, I. A. Assessment of Total Phenolic and Flavonoid Content, Antioxidant Properties, and Yield of Aeroponically and Conventionally Grown Leafy Vegetables and Fruit Crops: A Comparative Study. Evidence-Based Complement Alternat Med. 2014, 2014, 253875. https://doi.org/10.1155/2014/253875
Chauhan, A.; Banerjee, R. Evaluation of Traditional Uses, Phytochemical Constituents, Therapeutic Uses and Future Prospects of pyracantha Genus: A Systematic Review. Nat. Prod. Res. 2024, 39 (5) 922–934. https://doi.org/10.1080/14786419.2024.2319660
Chikalov, I.; Yao, P.; Moshkov, M.; Latombe, J. C. Learning Probabilistic Models of Hydrogen Bond Stability from Molecular Dynamics Simulation Trajectories. BMC Bioinformatics. 2011, 12 (SUPPL. 1), 1–6. https://doi.org/10.1186/1471-2105-12-S1-S34
Choo, M. Z. Y.; Chai, C. L. L. The Polypharmacology of Natural Products in Drug Discovery and Development. Annu. Rep. Med. Chem. 2023, 61, 55–100. https://doi.org/10.1016/bs.armc.2023.10.002
Chothani, S. R.; Dholariya, M. P.; Joshi, R. J.; Chamakiya, C. A.; Maliwal, D.; Pissurlenkar, R. R. S.; Patel, A. S.; Bhalodia, J. J.; Ambasana, M. A.; Patel, R. B.; Bapodra, A. H.; Kapuriya, N. P. Solvent-Free Synthesis, Biological Evaluation and in silico Studies of Novel 2-Amino-7-(Bis(2-Hydroxyethyl)Amino)-4H-Chromene-3-Carbonitrile Derivatives as Potential a-Amylase Inhibitors. J. Mol. Struct. 2024, 1301, 137462. https://doi.org/10.1016/j.molstruc.2023.137462
Das, A. P.; Mathur, P.; Agarwal, S. M. Machine Learning, Molecular Docking, and Dynamics-Based Computational Identification of Potential Inhibitors against Lung Cancer. ACS Omega. 2024, 9 (4), 4528–4539. https://doi.org/10.1021/acsomega.3c07338
Dewi, N. K. S. M.; Fakhrudin, N.; Wahyuono, S. A Comprehensive Review on the Phytoconstituents and Biological Activities of Nyctanthes arbor-tristis L. J. Appl. Pharm. Sci. 2022, 12 (8), 9–17. https://doi.org/10.7324/JAPS.2022.120802
Gautam, V. S.; Singh, A.; Kumari, P.; Nishad, J. H.; Kumar, J.; Yadav, M.; Bharti, R.; Prajapati, P.; Kharwar, R. N. Phenolic and Flavonoid Contents and Antioxidant Activity of an Endophytic Fungus Nigrospora sphaerica (EHL2), Inhabiting the Medicinal Plant Euphorbia Hirta (Dudhi) L. Arch. Microbiol. 2022, 204 (140), 1–13. https://doi.org/10.1007/s00203-021-02650-7
Hanwell, M. D.; Curtis, D. E.; Lonie, D. C.; Vandermeerschd, T.; Zurek, E.; Hutchison, G. R. Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform. J. Cheminform. 2012, 4 (8), 1–13. https://doi.org/10.1186/1758-2946-4-17
Hollingsworth, S. A.; Dror, R. O. Molecular Dynamics Simulation for All. Neuron 99. 2018, 6, 1129–1143. https://doi.org/10.1016/j.neuron.2018.08.011
Jain, P. K.; Pandey, A. The Wonder of Ayurvedic Medicine-Nyctanthes arbor-tristis. Int. J. Herb. Med. 2016, 9 (4), 9–17.
Khakurel, D.; Uprety, Y.; Ahn, G.; Cha, J. Y.; Kim, W. Y.; Lee, S. H.; Rajbhandary, S. Diversity, Distribution, and Sustainability of Traditional Medicinal Plants in Kaski District, Western Nepal. Front Pharmacol. 2022, 13, 1076351. https://doi.org/10.3389/fphar.2022.1076351
Kumar, S.; Saini, R.; Suthar, P.; Kumar, V.; Sharma, R. Plant Secondary Metabolites: Their Food and Therapeutic Importance. Plant Secondary Metabolites; Springer, Singapore, 2022, 371–2022. https://doi.org/10.1007/978-981-16-4779-6_12
Kunwar, R. M.; Baral, K.; Paudel, P.; Acharya, R. P.; Thapa-Magar, K. B.; Cameron, M.; Bussmann, R. W. Land-Use and Socioeconomic Change, Medicinal Plant Selection and Biodiversity Resilience in Far Western Nepal. PLoS One. 2016, 11 (12), 0167812. https://doi.org/10.1371/journal.pone.0167812
Kushwah, P.; Jain, G.; Patidar, A.; Baghel, J. S.; Agarwal, A. From Ancient Remedies to Modern Marvels: Unveiling the Medicinal Secrets of Nyctanthes arbor-tristis and Piper Betle Linn. Leaves- A Comprehensive Review. Int. J. Pharm. Sci. Med. 2023, 8 (12), 11–24. https://doi.org/10.47760/ijpsm.2023.v08i12.002
Laware, S. G.; Shirole, N. L. Formulation and Development of Polyherbal Ointment Containing Clerodendrum Serratum, Solanum Xanthocarpum, and Nyctanthes Arbort ristis Extracts and Assessment of Anti-Inflammatory Activity in Carrageenan-Induced Paw Edema Model. Int. J. Pharm. Qual. Assur. 2023, 14 (3), 523–528. https://doi.org/10.25258/ijpqa.14.3.10
Liu, M.; Hu, B.; Zhang, H.; Zhang, Y.; Wang, L.; Qian, H.; Qi, X. Inhibition Study of Red Rice Polyphenols on Pancreatic α-Amylase Activity by Kinetic Analysis and Molecular Docking. J. Cereal Sci. 2017A, 76, 186–192. https://doi.org/10.1016/j.jcs.2017.04.011
Liu, P.; Lu, J.; Yu, H.; Ren, N.; Lockwood, F. E.; Wang, Q. J. Lubricant Shear Thinning Behavior Correlated with Variation of Radius of Gyration via Molecular Dynamics Simulations. J. Chem. Phys. 2017B, 147 (8), 084904. https://doi.org/10.1063/1.4986552
Lolok, N.; Sumiwi, S. A.; Muhtadi, A.; Susilawati, Y.; Hendriani, R.; Ramadhan, D. S. F.; Levita, J.; Sahidin, I. Molecular Docking and Molecular Dynamics Studies of Bioactive Compounds Contained in Noni Fruit (Morinda citrifolia L.) against Human Pancreatic α-Amylase. J. Biomol. Struct. Dyn. 2022, 40 (15), 7091–7098. https://doi.org/10.1080/07391102.2021.1894981
Majumder, R.; Adhikari, L.; Hossain, C. M.; Dhara, M.; Sahu, J. Toxicological Evaluation, Brine Shrimp Lethality Assay, in vivo and ex vivo Antioxidant Assessment Followed by GC-MS Study of the Extracts Obtained from Olax Psittacorum (Lam.) Vahl. Orient. Pharm. Exp. Med. 2019, 1–23. https://doi.org/10.1007/s13596-019-00384-y
Martínez, L. Automatic Identification of Mobile and Rigid Substructures in Molecular Dynamics Simulations and Fractional Structural Fluctuation Analysis. PLoS One. 2015, 10 (3), 0119264. https://doi.org/10.1371/journal.pone.0119264
Meshram, M. M.; Rangari, S. B.; Kshirsagar, S. B.; Gajbhiye, S.; Trivedi, M. R.; Sahane, R. S. Nyctanthes arbor-tristis a Herbal Panacea. IJPSR. 2012, 3 (8), 2432–2440.
Meyer, B. N.; Ferrigni, N. A.; Putnam, J. E.; Jacobsen, L. B.; Nichols, D. E.; Mclaughlin, J. L. Brine Shrimp: A Convenient General Bioassay for Active Plant Constituents. J. Med. Plants. Res. 1982, 45, 31–34. https://doi.org/10.1055/s-2007-971236
Mishra, A. K.; Tiwari, K. N.; Saini, R.; Chaurasia, J. K.; Mishra, S. K. Assessment of Antioxidant Potential in Seed Extracts of Nyctanthes arbor-tristis L. and Phytochemical Profiling by Gas Chromatography-Mass Spectrometry System. Braz. J. Pharm. Sci., 2022, 58, e21180. https://doi.org/10.1590/s2175-97902022e21180
Mishra, A. K.; Upadhyay, R.; Chaurasia, J. K.; Tiwari, K. N. Comparative Antioxidant Study in Different Flower Extracts of Nyctanthes arbor-tristis (L.) (Oleaceae): an Important Medicinal Plant. Braz. J. Bot., 2016, 39, 813–820. https://doi.org/10.1007/s40415-016-0283-x
Mohamed, G. A.; Omar, A. M.; El-Araby, M. E.; Mass, S.; Ibrahim, S. R. M. Assessments of Alpha-Amylase Inhibitory Potential of Tagetes Flavonoids through in vitro, Molecular Docking, and Molecular Dynamics Simulation Studies. Int. J. Mol. Sci. 2023, 24 (12), 10195. https://doi.org/10.3390/ijms241210195
Mustafa, I.; Faisal, M. N.; Hussain, G.; Muzaffar, H.; Imran, M.; Ijaz, M. U.; Sohail, M. U.; Iftikhar, A.; Shaukat, A.; Anwar, H. Efficacy of Euphorbia Helioscopia in Context to a Possible Connection between Antioxidant and Antidiabetic Activities: A Comparative Study of Different Extracts. BMC Complement Med Ther. 2021, 21 (1), 1–12. https://doi.org/10.1186/s12906-021-03237-x
Naseem, N.; Khaliq, T.; Jan, S.; Nabi, S.; Sultan, P.; Hassan, Q. P.; Mir, F. A. An Overview on Pharmacological Significance, Phytochemical Potential, Traditional Importance and Conservation Strategies of Dioscorea deltoidea: A High Valued Endangered Medicinal Plant. Heliyon. 2024, 10 (10), e31245. https://doi.org/10.1016/j.heliyon.2024.e31245
Niksic, H.; Becic, F.; Koric, E.; Gusic, I.; Omeragic, E.; Muratovic, S.; Miladinovic, B.; Duric, K. Cytotoxicity Screening of Thymus Vulgaris L. Essential Oil in Brine Shrimp Nauplii and Cancer Cell Lines. Sci Rep. 2021, 11 (13178), 1–9. https://doi.org/10.1038/s41598-021-92679-x
Ogunyemi, O. M.; Gyebi, G. A.; Saheed, A.; Paul, J.; Nwaneri-Chidozie, V.; Olorundare, O.; Adebayo, J.; Koketsu, M.; Aljarba, N.; Alkahtani, S.; Batiha, G. E. S.; Olaiya, C. O. Inhibition Mechanism of Alpha-Amylase, a Diabetes Target, by a Steroidal Pregnane and Pregnane Glycosides Derived from Gongronema latifolium Benth. Front. Mol. Biosci. 2022, 9, 866719. https://doi.org/10.3389/fmolb.2022.866719
Olsson, T. S. G.; Williams, M. A.; Pitt, W. R.; Ladbury, J. E. The Thermodynamics of Protein-Ligand Interaction and Solvation: Insights for Ligand Design. J. Mol. Biol. 2008, 384 (4), 1002–1017. https://doi.org/10.1016/j.jmb.2008.09.073
Omar, A. M.; AlKharboush, D. F.; Mohammad, K. A.; Mohamed, G. A.; Abdallah, H. M.; Ibrahim, S. R. M. Mangosteen Metabolites as Promising Alpha-Amylase Inhibitor Candidates: In silico and in vitro Evaluations. Metabolites. 2022, 12 (12), 1239. https://doi.org/10.3390/metabo12121229
Onufriev, A. V; Case, D. A. Generalized Born Implicit Solvent Models for Biomolecules. Annu. Rev. Biophys. 2019, 48 (1), 275–298. https://doi.org/10.1146/annurev-biophys-052118-115325
Phuyal, N.; Jha, P. K.; Raturi, P. P.; Rajbhandary, S. Total Phenolic, Flavonoid Contents, and Antioxidant Activities of Fruit, Seed, and Bark Extracts of Zanthoxylum armatum DC. Sci. World J. 2020, 2020, 8780704. https://doi.org/10.1155/2020/8780704
Pires, D. E. V.; Blundell, T. L.; Ascher, D. B. PkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. J. Med. Chem. 2015, 58 (9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Proença, C.; Freitas, M.; Ribeiro, D.; Tomé, S. M.; Oliveira, E. F. T.; Viegas, M. F.; Araújo, A. N.; Ramos, M. J.; Silva, A. M. S.; Fernandes, P. A.; Fernandes, E. Evaluation of a Flavonoids Library for Inhibition of Pancreatic α-Amylase towards a Structure–Activity Relationship. J. Enzyme Inhib. Med. Chem. 2019, 34 (1), 577–588. https://doi.org/10.1080/14756366.2018.1558221
Rathore, A.; Juneja, R. K.; Tandon, J. S. An Iridoid Glucoside Form Nyctanthes arbor-tristis. Phytochemistry. 1989, 28 (7), 1913–1917. https://doi.org/10.1016/S0031-9422(00)97886-5
Rawat, H.; Verma, Y.; Saini, N.; Negi, N.; Pant, H. C.; Mishra, A. Nyctanthes arbor-tristis: A Traditional Herbal Plant with Miraculous Potential in Medicine. Int. J. Bot. Stud. 2021, 6 (3), 427–440.
Renganathan, S.; Manokaran, S.; Vasanthakumar, P.; Singaravelu, U.; Kim, P. S.; Kutzner, A.; Heese, K. Phytochemical Profiling in Conjunction with in vitro and in silico Studies to Identify Human α-Amylase Inhibitors in Leucaena leucocephala (Lam.) de Wit for the Treatment of Diabetes Mellitus. ACS Omega. 2021, 6 (29), 19045–19057. https://doi.org/10.1021/acsomega.1c02350
Sabudak, T.; Demirkiran, O.; Ozturk, M.; Topcu, G. Phenolic Compounds from Trifolium echinatum Bieb. and Investigation of Their Tyrosinase Inhibitory and Antioxidant Activities. Phytochemistry. 2013, 96, 305–311. https://doi.org/10.1016/j.phytochem.2013.08.014
Sah, A. K.; Verma, V. K. Phytochemicals and Pharmacological Potential of Nyctanthes arbor-tristis: A Comprehensive Review. Int. J. Res. Pharm. Biomed. Sci. 2012, 3 (1), 420–427.
Sethi, S.; Joshi, A.; Arora, B.; Bhowmik, A.; Sharma, R. R.; Kumar, P. Significance of FRAP, DPPH, and CUPRAC Assays for Antioxidant Activity Determination in Apple Fruit Extracts. Eur. Food Res. Technol. 2020, 246 (3), 591–598. https://doi.org/10.1007/s00217-020-03432-z
Shaweta, S.; Akhil, S.; Utsav, G. Molecular Docking Studies on the Anti-Fungal Activity of Allium Sativum (Garlic) against Mucormycosis (Black Fungus) by BIOVIA Discovery Studio Visualizer 21.1.0.0. Ann. Antivir Antiretrovir. 2021, 5 (1), 28–32. https://doi.org/https://doi.org/10.21203/rs.3.rs-888192/v1
Shrestha, T.; Maharjan, B.; Panta, R.; Lal Swagat Shrestha, R.; Parajuli, N.; Neupane, P.; Dhital, S.; Bharati, S.; Adhikari Subin, J.; Marasini, P. Molecular Docking and ADMET Prediction of Compounds from Piper Longum L. Detected by GC-MS Analysis in Diabetes Management. Mor. J. Chem. 2024, 2024 (2), 776–798. https://doi.org/10.48317/IMIST.PRSM/morjchem-v12i2.46845
Solanki, M.; Rajhans, S.; Pandya, H. A.; Mankad, A. U. Nyctanthes arbor-tristis Linn: A Short Review. World J. Pharm. Pharm. Sci. 2021, 10 (3), 1047–1054. https://doi.org/10.20959/wjpps20213-18575
Stănciuc, N.; Râpeanu, G.; Bahrim, G. E.; Aprodu, I. The Interaction of Bovine β-Lactoglobulin with Caffeic Acid: From Binding Mechanisms to Functional Complexes. Biomolecules. 2020, 10 (8), 1–14. https://doi.org/10.3390/biom10081096
Sugandh, F.; Chandio, M.; Raveena, F.; Kumar, L.; Karishma, F.; Khuwaja, S.; Memon, U. A.; Bai, K.; Kashif, M.; Varrassi, G.; Khatri, M.; Kumar, S. Advances in the Management of Diabetes Mellitus: A Focus on Personalized Medicine. Cureus. 2023, 15 (8), e43697. https://doi.org/10.7759/cureus.43697
Trott, O.; Olson, A. J. AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. J. Comput. Chem. 2009, 31, 455-461. https://doi.org/10.1002/jcc.21334
Vasanthkumar, J.; Hulikal, A.; Santoshkumar, S.; Sripathy, H. In silico Docking Studies of α Amylase Inhibitors from the Anti Diabetic Plant Leucas ciliata Benth and an Endophyte, Streptomyces longisporoflavus. 3 Biotech. 2021, 11 (2), 1–16. https://doi.org/10.1007/s13205-020-02547-0
Vishwakarma, R. K.; Negi, A.; Negi, D. S. Abortitristoside A and Desrhamnosylverbanscoside: The Potential COX-2 Inhibitor from the Leaves of Nyctanthes arbor-tristis as Anti-Inammatory Agents Based on the in vitro Assay, Molecular Docking and ADMET Prediction. Chem. Pap. 2022, 77 (6), 3035-3049. https://doi.org/10.21203/rs.3.rs-1345800/v2
Wang, E.; Sun, H.; Wang, J.; Wang, Z.; Liu, H.; Zhang, J. Z. H.; Hou, T. End-Point Binding Free Energy Calculation with MM/PBSA and MM/GBSA: Strategies and Applications in Drug Design. Chem. Rev. 2019, 119, 9478–9508. https://doi.org/10.1021/acs.chemrev.9b00055
Yang, Y.; Karakhanova, S.; Hartwig, W.; D’Haese, J. G.; Philippov, P. P.; Werner, J.; Bazhin, A. V. Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy. J. Cell Physiol. 2016, 231 (12), 2570–2581. https://doi.org/10.1002/jcp.25349
Yi, J.; Zhao, T.; Zhang, Y.; Tan, Y.; Han, X.; Tang, Y.; Chen, G. Isolated Compounds from Dracaena Angustifolia Roxb and Acarbose Synergistically/Additively Inhibit α-Glucosidase and α-Amylase: An in vitro Study. BMC Complement Med Ther. 2022, 22 (177), 1–12. https://doi.org/10.1186/s12906-022-03649-3
Yuan, S.; Chan, H. C. S.; Hu, Z. Using PyMOL as a Platform for Computational Drug Design. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2017, 7, 1298. https://doi.org/10.1002/wcms.1298
Zahra, S.; Zaib, S.; Khan, I. Identification of Isobenzofuranone Derivatives as Promising Antidiabetic Agents: Synthesis, in vitro and in vivo Inhibition of α-Glucosidase and α-Amylase, Computational Docking Analysis and Molecular Dynamics Simulations. Int. J. Biol. Macromol. 2024, 259 (2), 129241. https://doi.org/10.1016/j.ijbiomac.2024.129241
Zain, S. N. D. M.; Omar, W. A. W. Antioxidant Activity, Total Phenolic Content and Total Flavonoid Content of Water and Methanol Extracts of Phyllanthus Species from Malaysia. Pharmacogn J. 2018, 10 (4), 677–681. https://doi.org/10.5530/pj.2018.4.111
Zerdan, M. B.; Moussa, S.; Atoui, A.; Assi, H. I. Mechanisms of Immunotoxicity: Stressors and Evaluators. Int. J. Mol. Sci. 2021, 22 (15), 8242. https://doi.org/10.3390/ijms22158242
Zhang, D.; Lazim, R. Application of Conventional Molecular Dynamics Simulation in Evaluating the Stability of Apomyoglobin in Urea Solution. Sci. Rep. 2017, 7, 44651. https://doi.org/10.1038/srep44651
Zhao, Y.; Wang, M.; Huang, G. Structure-Activity Relationship and Interaction Mechanism of Nine Structurally Similar Flavonoids and α-Amylase. J. Funct. Foods. 2021, 86, 104739. https://doi.org/10.1016/j.jff.2021.104739
Zoete, V.; Cuendet, M. A.; Grosdidier, A.; Michielin, O. SwissParam: A Fast Force Field Generation Tool for Small Organic Molecules. J. Comput. Chem. 2011, 32 (11), 2359–2368. https://doi.org/10.1002/jcc.21816
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