Anti-inflammatory effects of 7-methoxycryptopleurine and structure-activity relations of phenanthroindolizidines and phenanthroquinolizidines.
A cryptopleurine analogue, 7-methoxycryptopleurine, a phenanthroquinolizidine, was first found to exert potent anti-inflammatory activity in vitro and in vivo as well as have remarkable cytotoxic activity against cancer cells. The non-planar structure between the two major moieties, phenanthrene and indolizidine/quinolizidine, played a crucial role in the activity of phenanthroindolizidines or phenanthroquinolizidines in terms of cytotoxic effects on cancer cells and anti-inflammatory activity. We also showed that increase in planarity and rigidity of the indolizidine/quinolizidine moiety and change of the amine group into an amide by introducing a keto group to phenanthroindolizidines or phenanthroquinolizidines at the equivalent position 9 of tylophorine significantly reduced their activities. Moreover, in general, phenanthroquinolizidines are more potent than their respective phenanthroindolizines.
Yang
Cheng-Wei
CW
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli county, Taiwan, ROC.
Chuang
Ta-Hsien
TH
Wu
Pei-Lin
PL
Huang
Wen-Hsin
WH
Lee
Shiow-Ju
SJ
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D006801:Humans; D007212:Indolizines / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010616:Phenanthrenes / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C518787:7-methoxycryptopleurine; D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D007212:Indolizines; D010616:Phenanthrenes; D011807:Quinolizines; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; C004218:tylophorine