Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors.
A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a-f and 7,8-dehydrorutaecarpine 5a-c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a-c, were synthesized and subjected to pharmacological evaluation as acetylcholinesterase (AChE) inhibitors. The synthetic compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.
Wang
Bin
B
School of Pharmaceutical Sciences, Sun Yat-sen University, Waihuan East Road 132, Guangzhou 510006, People's Republic of China.
Mai
Yi-Chi
YC
Li
Yue
Y
Hou
Jin-Qiang
JQ
Huang
Shi-Liang
SL
Ou
Tian-Miao
TM
Tan
Jia-Heng
JH
An
Lin-Kun
LK
Li
Ding
D
Gu
Lian-Quan
LQ
Huang
Zhi-Shu
ZS
D000110:Acetylcholinesterase / Q000187:drug effects; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D052999:Quinazolinones
D000110:Acetylcholinesterase; D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D026121:Indole Alkaloids; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones