Hypoglycemic effects of multiflorine derivatives in normal mice.
(-)-Multiflorine isolated from leguminous plants produces a hypoglycemic effect when administered to mice with streptozotocin-induced diabetes. (-)-Multiflorine has an enaminone-type conjugation on the A ring, which is unusual in lupine alkaloids. Proceeding on the assumption that the A-B ring is responsible for the hypoglycemic effect, several compounds bearing the quinolizidin-2-one ring system were synthesized, and their hypoglycemic effects were examined. In addition, tricyclic compounds bearing 4-pyridone were synthesized, and their hypoglycemic effects were examined. The hypoglycemic effect of a 4-pyridone-type compound was similar to that of (-)-multiflorine as measured by oral glucose tolerance testing in normal mice. No hypoglycemic effect of a 4-piperidone-type compound was observed. These results indicate that compounds possessing double bond(s) in the A ring of multiflorine may be lead compounds for a new type of diabetes drug.
Kubo
Hajime
H
Institute of Medicinal Chemistry, Hoshi University, Ebara, Tokyo, Japan. kubo@hoshi.ac.jp
Inoue
Mai
M
Kamei
Junzo
J
Higashiyama
Kimio
K
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D007004:Hypoglycemic Agents; D011728:Pyridones; C417683:multiflorine; D000093843:Quinolizidine Alkaloids