Studies on cardiac ingredients of plants. VII: Chemical transformation of proscillaridin by means of the Diels-Alder reaction and biological activities of its derivatives.
The Diels-Alder reactions of a cardiac glycoside, proscillaridin (1), with some dienophiles were investigated. The reaction of 1 with alkenes such as methyl vinyl ketone and methyl acrylate afforded 3-oxo-2-oxabicyclo[2.2.2]oct-7-enes (2-5) and para-substituted benzene derivatives (6 and 7), while 1 reacted with alkynes (3-butyn-2-one, methyl propiolate) to yield para- or meta-substituted benzene derivatives (6-9). The biological activities of the resulting derivatives were evaluated by the use of isolated guinea-pig papillary muscle preparations and Na+,K(+)-adenosine triphosphatase (ATPase) preparation from dog kidney. Among the proscillaridin derivatives, compounds 4 and 7 moderately inhibited Na+,K(+)-ATPase activity. Furthermore, the concentration range of 7 over which its positive inotropic effect on guinea-pig papillary muscle preparations, increased from 5% to 95% of maximum was broader than that of 1, i.e., concentration dependency was maintained over a greater range of concentration.
Murakami
N
N
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Tanase
T
T
Nagai
S
S
Sato
Y
Y
Ueda
T
T
Sakakibara
J
J
Ando
H
H
Hotta
Y
Y
Takeya
K
K
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D004285:Dogs; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D011442:Proscillaridin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology
D000251:Adenosine Triphosphatases; D011442:Proscillaridin