[Vasorelaxant activity of N-caffeoylamino acids].
Twelve N-caffeoylamino acids and N-cinnamoylamino acids were synthesized and their vasorelaxation activity against norepinephrine (NE)-induced contraction of rat aorta was examined. The following structure-activity relationships were found. 1) On the benzene ring, the caffeoyl structure is effective for vasorelaxation, while the cinnamoyl structure reduced vasorelaxation activity. 2) Four to six carbons are more effective as the carbon chain connecting the acylamino and carboxyl terminal groups. N-Caffeoyl-beta-alanine and N-caffeoyltranexamic acid were used to investigate the action mechanism of vasorelaxing activities. It is believed that these compounds antagonize NE-induced vasocontraction by inhibiting receptor-operated calcium channels.
Iizuka
Toru
T
Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. iizuka@hoshi.ac.jp
Funayama
Hiroko
H
Kusano
Genjiro
G
Nagai
Masahiro
M
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology*
D002109:Caffeic Acids; D015220:Calcium Channels; D002934:Cinnamates; D014665:Vasodilator Agents; D009638:Norepinephrine