| Title : Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase - Zhu_2013_Bioorg.Med.Chem_21_4218 |
| Author(s) : Zhu J , Wu CF , Li X , Wu GS , Xie S , Hu QN , Deng Z , Zhu MX , Luo HR , Hong X |
| Ref : Bioorganic & Medicinal Chemistry , 21 :4218 , 2013 |
| Abstract : A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BCHE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BCHE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BCHE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100muM of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face pi-pi stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09A) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BCHE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BCHE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BCHE, potentially useful to treat neurodegenerative diseases. |
| ESTHER : Zhu_2013_Bioorg.Med.Chem_21_4218 |
| PubMedSearch : Zhu_2013_Bioorg.Med.Chem_21_4218 |
| PubMedID: 23719283 |
Zhu J, Wu CF, Li X, Wu GS, Xie S, Hu QN, Deng Z, Zhu MX, Luo HR, Hong X (2013)
Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase
Bioorganic & Medicinal Chemistry
21 :4218
Zhu J, Wu CF, Li X, Wu GS, Xie S, Hu QN, Deng Z, Zhu MX, Luo HR, Hong X (2013)
Bioorganic & Medicinal Chemistry
21 :4218