Design, synthesis, and biological evaluation of new territrem B analogues.
Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined.
Jiang
Xiangrui
X
Department of Traditional Chinese Medicine and Natural Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, PR China.
Ao
Lei
L
Zhou
Changxin
C
Yang
Leixiang
L
Zhang
Qijun
Q
Li
Haibo
H
Sun
Lianli
L
Wu
Xiumei
X
Bai
Hua
H
Zhao
Yu
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011714:Pyrans / Q000737:chemistry*
D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D011714:Pyrans; C040405:territrem B