| Autor: |
Cuong NM; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam.; Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam., Khanh PN; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam.; Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam., Nhung LTH; Faculty of Chemical Technology, Hanoi University of Industry, Bac Tu Liem District, Hanoi, Vietnam., Ha NX; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam., Huong TT; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam., Bauerova K; Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Karlova Ves, Slovakia., Kim YH; College of Pharmacy, Chungnam National University, Daejeon, South Korea., Tung DD; Saint Paul General Hospital, Hanoi, Vietnam., Thuy TT; Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam.; Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam., Anh NTH; Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam.; Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam. |
| Abstrakt: |
From the root bark of Pinus krempfii Lecomte, four flavonoids were isolated and evaluated for their inhibitory activities against AChE and BChE enzymes in vitro and in silico . Tectochrysin ( 1 ) was found to inhibit AChE with an IC 50 value of 33.69 ± 2.80 μM. The docking study results also showed agreement with the in vitro test results. All four compounds also showed the best binding affinity for the AChE enzyme, characterised by binding energy (ΔG) values as low as -8.1 to -9.3 kcal/mol, in which, the compound tectochrysin had the best binding affinity for the AChE protein with a ΔG value of -9.329 kcal/mol. Tectochrysin ( 1 ) was also bound to the amino acid Phe295 of AChE with a bond length of 2.8 Å, similar to the control dihydrotanshinone-I. Galangin ( 2 ) also showed its in vitro inhibitory activity against BChE with an IC 50 value of 82.21 ± 2.70 μM. In silico , it also had the best binding energy value of -9.072 kcal/mol with BChE and formed hydrogen bonds with the His438 (2.85 Å) residues of BChE like the positive control (tacrine). The steered molecular dynamics (SMD) simulation results of these two complexes revealed a mechanistic insight that the protein-ligand complexes showed stable trajectories throughout the 20 and 150 ns simulations. Moreover, the drug likeliness suggested that both flavonoids ( 1 and 2 ) were expected to be drug-like and have an LD 50 toxicity level of 5. This study has contributed new results for drug discovery and the development of substances with neuroprotective effects, especially for the treatment of Alzheimer's disease.Communicated by Ramaswamy H. Sarma. |
