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| Format: | Artículo científico |
| Sprache: | en |
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Marine drugs
2025
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| Online-Zugang: | https://pubmed.ncbi.nlm.nih.gov/41440905/ |
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| author | Sigera, Sachini Theekshana, Kavindu D Dinanja, Sathmi G Eranga, Pasindu Karunathilake, Nayanatharie Abeywardhana, Shamali Weerasinghe, Laksiri Senapathi, Tharindu Peiris, Dinithi C |
| author_facet | Sigera, Sachini Theekshana, Kavindu D Dinanja, Sathmi G Eranga, Pasindu Karunathilake, Nayanatharie Abeywardhana, Shamali Weerasinghe, Laksiri Senapathi, Tharindu Peiris, Dinithi C Sigera, Sachini Theekshana, Kavindu D Dinanja, Sathmi G Eranga, Pasindu Karunathilake, Nayanatharie Abeywardhana, Shamali Weerasinghe, Laksiri Senapathi, Tharindu Peiris, Dinithi C |
| collection | PubMed - marine biology |
| contents | Molecular Docking and Dynamics Simulations Reveal the Antidiabetic Potential of a Novel Fucoxanthin Derivative from . Sigera, Sachini Theekshana, Kavindu D Dinanja, Sathmi G Eranga, Pasindu Karunathilake, Nayanatharie Abeywardhana, Shamali Weerasinghe, Laksiri Senapathi, Tharindu Peiris, Dinithi C Molecular Docking Simulation Xanthophylls Molecular Dynamics Simulation Hypoglycemic Agents alpha-Amylases Phaeophyceae alpha-Glucosidases Diabetes Mellitus, Type 2 Glycoside Hydrolase Inhibitors Animals Humans Acarbose Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder requiring safer and more effective therapeutic alternatives. This study investigates a novel fucoxanthin derivative isolated from the marine brown alga using a comprehensive in silico approach. Molecular docking revealed that the derivative exhibited higher binding affinities toward α-amylase (-9.4 kcal/mol) and α-glucosidase (-8.0 kcal/mol) compared to the reference drug acarbose (-8.5 and -7.4 kcal/mol, respectively). Pharmacokinetic analysis predicted good intestinal absorption and P-gp inhibition (0.894) and moderate plasma clearance (7.864 mL/min/kg), while toxicity predictions classified it in toxicity class 3, with no respiratory or ocular toxicity. Drug-likeness evaluation showed only one Lipinski and one Veber rule violation, common for natural products. Molecular dynamics simulations conducted for 100 ns using NAMD 3.0 confirmed stable protein-ligand complexes with average RMSD values of ~1.3 Å and ~1.8 Å for α-amylase and α-glucosidase, respectively, and consistent hydrogen bonding profiles. Structural analysis identified a substitution of the allene bond with an unsaturated ketone at the C8' position as a key contributor to enhanced enzyme interaction. The findings suggest that this fucoxanthin derivative is a promising natural candidate for T2DM therapy and warrants further investigation through lab experiments (in vitro and in vivo). |
| format | Artículo científico |
| id | pubmed_41440905 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Marine drugs |
| record_format | pubmed |
| spellingShingle | Molecular Docking and Dynamics Simulations Reveal the Antidiabetic Potential of a Novel Fucoxanthin Derivative from . Sigera, Sachini Theekshana, Kavindu D Dinanja, Sathmi G Eranga, Pasindu Karunathilake, Nayanatharie Abeywardhana, Shamali Weerasinghe, Laksiri Senapathi, Tharindu Peiris, Dinithi C Molecular Docking Simulation Xanthophylls Molecular Dynamics Simulation Hypoglycemic Agents alpha-Amylases Phaeophyceae alpha-Glucosidases Diabetes Mellitus, Type 2 Glycoside Hydrolase Inhibitors Animals Humans Acarbose Molecular Docking and Dynamics Simulations Reveal the Antidiabetic Potential of a Novel Fucoxanthin Derivative from . Sigera, Sachini Theekshana, Kavindu D Dinanja, Sathmi G Eranga, Pasindu Karunathilake, Nayanatharie Abeywardhana, Shamali Weerasinghe, Laksiri Senapathi, Tharindu Peiris, Dinithi C Molecular Docking Simulation Xanthophylls Molecular Dynamics Simulation Hypoglycemic Agents alpha-Amylases Phaeophyceae alpha-Glucosidases Diabetes Mellitus, Type 2 Glycoside Hydrolase Inhibitors Animals Humans Acarbose Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder requiring safer and more effective therapeutic alternatives. This study investigates a novel fucoxanthin derivative isolated from the marine brown alga using a comprehensive in silico approach. Molecular docking revealed that the derivative exhibited higher binding affinities toward α-amylase (-9.4 kcal/mol) and α-glucosidase (-8.0 kcal/mol) compared to the reference drug acarbose (-8.5 and -7.4 kcal/mol, respectively). Pharmacokinetic analysis predicted good intestinal absorption and P-gp inhibition (0.894) and moderate plasma clearance (7.864 mL/min/kg), while toxicity predictions classified it in toxicity class 3, with no respiratory or ocular toxicity. Drug-likeness evaluation showed only one Lipinski and one Veber rule violation, common for natural products. Molecular dynamics simulations conducted for 100 ns using NAMD 3.0 confirmed stable protein-ligand complexes with average RMSD values of ~1.3 Å and ~1.8 Å for α-amylase and α-glucosidase, respectively, and consistent hydrogen bonding profiles. Structural analysis identified a substitution of the allene bond with an unsaturated ketone at the C8' position as a key contributor to enhanced enzyme interaction. The findings suggest that this fucoxanthin derivative is a promising natural candidate for T2DM therapy and warrants further investigation through lab experiments (in vitro and in vivo). |
| title | Molecular Docking and Dynamics Simulations Reveal the Antidiabetic Potential of a Novel Fucoxanthin Derivative from . |
| topic | Molecular Docking Simulation Xanthophylls Molecular Dynamics Simulation Hypoglycemic Agents alpha-Amylases Phaeophyceae alpha-Glucosidases Diabetes Mellitus, Type 2 Glycoside Hydrolase Inhibitors Animals Humans Acarbose |
| url | https://pubmed.ncbi.nlm.nih.gov/41440905/ |