Title : Selective acetylcholinesterase inhibitors derived from muscle relaxant dantrolene - Aoyama_2019_Bioorg.Med.Chem.Lett__126888 |
Author(s) : Aoyama H , Doura T |
Ref : Bioorganic & Medicinal Chemistry Lett , :126888 , 2019 |
Abstract :
Dantrolene, the only therapeutic agent for malignant hyperthermia, is known to have not only a muscle relaxant effect, but also a neuroprotective effect and Alzheimer's disease improving effect. Recently, it has been reported that dantrolene has a weak inhibitory effect on acetylcholinesterase (AChE), which is a therapeutic drug target for Alzheimer's disease. Thus, we focused on developing of AChE inhibitors with benzylpiperidine/piperazine moieties that are based on the dantrolene skeleton. Several derivatives showed an inhibitory activity. Among them, ortho-nitro derivative 8c showed the most potent inhibitory activity with the IC50 value of 34.2 nM. Furthermore, Lineweaver-Burk plot analysis indicated that 8c is AChE-selective inhibitor, which shows only a weak inhibitory effect on butyrylcholinesterase (BuChE) and a non-competitive inhibition. |
PubMedSearch : Aoyama_2019_Bioorg.Med.Chem.Lett__126888 |
PubMedID: 31901380 |
Aoyama H, Doura T (2019)
Selective acetylcholinesterase inhibitors derived from muscle relaxant dantrolene
Bioorganic & Medicinal Chemistry Lett
:126888
Aoyama H, Doura T (2019)
Bioorganic & Medicinal Chemistry Lett
:126888