Title : Design and development of 1,3,4-oxadiazole derivatives as potential inhibitors of acetylcholinesterase to ameliorate scopolamine-induced cognitive dysfunctions - Mishra_2019_Bioorg.Chem_89_103025 |
Author(s) : Mishra P , Sharma P , Tripathi PN , Gupta SK , Srivastava P , Seth A , Tripathi A , Krishnamurthy S , Shrivastava SK |
Ref : Bioorg Chem , 89 :103025 , 2019 |
Abstract :
The novel hybrids bearing 4-aminopyridine (4-AP) tethered with substituted 1,3,4-oxadiazole nucleus were designed, synthesized, and evaluated for their potential AChE inhibitory property along with significant antioxidant potential. The inhibitory potential (IC50) of synthesized analogs was evaluated against human cholinesterases (hAChE and hBChE) using Ellman's method. Among all the compounds, 9 with 4-hydroxyl substituent showed maximum hAChE inhibition with the non-competitive type of enzyme inhibition (IC50=1.098microM; Ki=0.960microM). Further, parallel artificial membrane permeation assay (PAMPA-BBB) showed significant BBB permeability in most of the synthesized compounds. Meanwhile, compound 9 also inhibited AChE-induced Abeta aggregation (38.2-65.9%) by thioflavin T assay. The in vivo behavioral studies showed dose-dependent improvement in learning and memory by compound 9. The ex vivo studies also affirmed the significant AChE inhibition and antioxidant potential of compound 9 in brain homogenates. |
PubMedSearch : Mishra_2019_Bioorg.Chem_89_103025 |
PubMedID: 31176239 |
Inhibitor | 4-aminopyridine-1,3,4-oxadiazole-9 |
Mishra P, Sharma P, Tripathi PN, Gupta SK, Srivastava P, Seth A, Tripathi A, Krishnamurthy S, Shrivastava SK (2019)
Design and development of 1,3,4-oxadiazole derivatives as potential inhibitors of acetylcholinesterase to ameliorate scopolamine-induced cognitive dysfunctions
Bioorg Chem
89 :103025
Mishra P, Sharma P, Tripathi PN, Gupta SK, Srivastava P, Seth A, Tripathi A, Krishnamurthy S, Shrivastava SK (2019)
Bioorg Chem
89 :103025