Preliminary structure-antiangiogenic activity relationships of 4-senecioyloxymethyl-6,7-dimethoxycoumarin.
Through a systematic modification of the novel angiogenesis inhibitor 4-senecioyloxymethyl-6,7-dimethoxycoumarin (1) we found that a 6,7-dimethoxy moiety is important for bioactivity of 1. Replacement of the lactone functionality in coumarin 1 by an amide decreased its activity. By substitution of the senecioyl chain with various cinnamoyl groups we discovered 6d, bearing a 4-methoxycinnamoyl instead of senecioyl side chain, with inhibitory activity in HUVEC tube formation assay enhanced by one order of magnitude compared to 1. We have also synthesized compound 12, an analogue of 6d, with equipotency and improved water solubility.
Nam
Nguyen-Hai
NH
College of Pharmacy, Chungnam National University, Taejon, Republic of Korea.
Kim
Yong
Y
You
Young-Jae
YJ
Hong
Dong-Ho
DH
Kim
Hwan-Mook
HM
Ahn
Byung-Zun
BZ
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology; D031407:Crinum / Q000737:chemistry; D006801:Humans; D028321:Plant Preparations; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000187:drug effects
C475709:4-senecioyloxymethyl-6,7-dimethoxycoumarin; D020533:Angiogenesis Inhibitors; D003374:Coumarins; D028321:Plant Preparations