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Synthesis, in vitro Acetylcholinesterase Inhibitory Activity Evaluation and Docking Investigation of Some Aromatic Chalcones

Original Research
  • Thanh-Dao Tran, Thai-Son Tran, Thi-Cam-Vi Nguyen, Minh-Tri Le, Khac-Minh Thai,
  • Pages 15-25

In this study, a total of twenty chalcones were synthesized via Claisen-Schmidt condensation reaction and evaluated for their in vitro acetylcholinesterase inhibitory activities using Ellman’s method. Molecular docking studies on acetylcholinesterase were performed to elucidate the interactions between these chalcone derivatives and acetylcholinesterase active site at the molecular level. From the series, six compounds (S1-5 and S17) exhibited strong acetylcholinesterase inhibitory activities with IC50 values below 100 µM compared to the parent unsubstituted chalcone. Compound S17 (4’-amino-2-chlorochalcone) showed the strongest acetylcholinesterase inhibitory activity in the investigated group with IC50 value of 36.10 µM. Molecular modeling studies were consistent with the results of in vitro acetylcholinesterase inhibitory activities, and chalcone S17 could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors.

Graphical abstract

Virtual Screening, Oriented-synthesis and Evaluation of Lipase Inhibitory Activity of Benzyl Amino Chalcone Derivatives

Original Research
  • Trang Hoang Minh Vu, Duy Duc Vu, Dat Van Truong, Phuong Thuy Viet Nguyen, Dao Thanh Tran,
  • Pages 26-36
  • 21/12/2017
  • 124
  • 993
  • Free

Nowadays, obesity has been becoming one of the most popular problems to the global health. Molecular design with the aid of computing method is an efficient and cost-saving solution in the initial research of new potential drugs for the treatment of obesity. This study focused on benzyl amino chalcone derivatives as they have a benzyl group that can mimic the hydrophobic effect of the long chain carbon of Orlistat, a drug used to treat obesity. Initially, 102 molecular structures were prepared and docked into the protein by using AutoDock Vina version 1.5.6. Fourteen structures having good docking scores were selected to synthesize using a Claisen-Schmidt reaction. Afterward, these synthesized chalcones were tested biological activity against pancreatic lipase by spectrophotometric determination at a wavelength of 405 nm, using p-nitro phenyl palmitate as the substrate. The co-crystallized ligand of pancreatic lipase enzyme was redocked into the enzyme and the RMSD was 1.4976 Å which showed the ligand and the protein preparation could regenerate the practical experiment. As the docking results, the binding affinities of top ten compounds varied from -8.6 and -10.2 kcal/mol. Biological testing resulted in 4 derivatives with IC50 >120 µM, 8 derivatives with 60 µM < IC50 < 120 µM and 2 derivatives with IC50 < 60 µM. In addition, the docking results also confirmed the key role of amino acid Ser152 in interacting with the ligands. The benzyl amino chalcone derivatives are required for further investigation to become a lead compound for anti-obesity drug discovery.

Graphical abstract