Evaluation of canthinone alkaloids as cerebral protective agents.
Considerable attention has been paid to cerebral protective drugs as a potential therapy for dementia. Screening of a natural compound library here resulted in identification of five canthinone alkaloids, viz., picrasidine L (1), picrasidine O (2), eurycomine E (3), 3-ethyl-canthin-5,6-dione (4), and 3-ethyl-4-methoxy-canthin-5,6-dione (5), as novel cerebral protective agents. The structure-activity relationship indicated that C-4, C-9, and N-3 substitutions greatly affected their cerebral protective effect. Among these, compound 2 exhibited a cerebral protective effect through suppressing neuronal hyperexcitability due to an increase in the excitatory neurotransmitter glutamic acid. Furthermore, compound 2 did not affect heart rate and mean systolic blood pressure. This investigation suggests that compound 2 has potential for further development as a cerebral protective drug.
Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
Tatsunori
T
Sasaki
Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan. Electronic address: liwei@phar.toho-u.ac.jp.
Wei
W
Li
Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
Taichi
T
Ohmoto
Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan. Electronic address: koike@phar.toho-u.ac.jp.
Kazuo
K
Koike
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002545:Brain Ischemia / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D005849:Gerbillinae; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D026121:Indole Alkaloids; D018696:Neuroprotective Agents
Alkaloid; Canthinone; Cerebral protective effect; Dementia; Picrasidine O