A new aspect of view in synthesizing new type beta-adrenoceptor blockers with ancillary antioxidant activities.
A series of vanilloid-type beta-adrenoceptor blockers derived from antioxidant traditional Chinese herbal medicines were synthesized and tested for their antioxidant and adrenoceptor antagonistic activities. They all possessed significant beta-adrenoceptor blocking activities under in vitro experiments and radioligand binding assays. In addition, some compounds were further examined in in vivo tests and produced antagonist effects matching that of propranolol and labetalol by measurements of antagonism toward (-)isoproterenol-induced tachycardia and (-)phenylephrine-induced pressor responses in anesthetized rats. Furthermore, all of the compounds had antioxidant effects inherited from their original structures. In conclusion, compound 11 had the most potent beta-adrenoceptors blocking activity, 12 and 13 possessed high cardioselectivity, whereas 14, 15 and 16 possessed additional alpha-adrenoceptor blocking activity and 15 is the most effective antioxidant of all. The antioxidant activity may be due to their alpha and beta unsaturated side chain at position 1 and ortho-substituted methoxy moiety on 4-phenoxyethylamine.
Huang
Y C
YC
Development Center for Biotechnology, 81 Chang-Hsing Street, Taipei 106, Taiwan.
Wu
B N
BN
Yeh
J L
JL
Chen
S J
SJ
Liang
J C
JC
Lo
Y C
YC
Chen
I J
IJ
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D009682:Magnetic Resonance Spectroscopy; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants