1. Design, microwave synthesis, and molecular docking studies of catalpol crotonates as potential neuroprotective agent of diabetic encephalopathy.
- Author
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Liu S, Cheng X, Li X, Kong Y, Jiang S, Dong C, and Wang G
- Subjects
- Binding Sites, Brain Diseases drug therapy, Brain Diseases enzymology, Brain Diseases etiology, Cell Line, Tumor, Cell Survival drug effects, Crotonates chemical synthesis, Diabetes Complications drug therapy, Diabetes Complications enzymology, Diabetes Mellitus drug therapy, Diabetes Mellitus enzymology, Glutathione Peroxidase chemistry, Glutathione Peroxidase metabolism, Humans, Hydrogen Bonding, Hypoglycemic Agents chemical synthesis, Iridoid Glucosides chemical synthesis, Microwaves, Models, Molecular, Molecular Docking Simulation, Molecular Dynamics Simulation, Neurons drug effects, Neurons metabolism, Neurons pathology, Neuroprotective Agents chemical synthesis, Protein Binding, Crotonates pharmacology, Glutathione Peroxidase antagonists & inhibitors, Hypoglycemic Agents pharmacology, Iridoid Glucosides pharmacology, Neuroprotective Agents pharmacology
- Abstract
Catalpol has gained increasing attention for its potential contributions in controlling glycolipid metabolism and diabetic complications, which makes used as a very promising scaffold for seeking new anti-diabetic drug candidates. Acylation derivatives of catalpol crotonate (CCs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surfex-Docking method. Catalpol hexacrotonate (CC-6) was synthesized using microwave assisted method and characterized by FT-IR, NMR, HPLC and HRMS. The MD results indicate that with the increasing of esterification degree of hydroxyl, the C log P of CCs increased significantly, and the calculated total scores (Total_score) of CCs are all higher than that of catalpol. It shows that CCs maybe served as potential lead compounds for neuroprotective agents. It was found that the maximum Total_score of isomers in one group CCs is often not that the molecule with minimum energy. MD calculations show that there are five hydrogen bonds formed between CC-6 and the surrounding amino acid residues. Molecular dynamics simulation results show that the binding of CC-6 with GSH-Px is stable. CC-6 was screened for SH-SY5Y cells viability by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, the result indicates CC-6 can effectively reverse SZT induced cells apoptosis with dose-dependent manner, which can indirectly show that CC-6 is a potential neuroprotective agent.
- Published
- 2020
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