Antihyperglycemic activities of cryptolepine analogues: an ethnobotanical lead structure isolated from Cryptolepis sanguinolenta.
Cryptolepine (1) is a rare example of a natural product whose synthesis was reported prior to its isolation from nature. In the previous paper we reported the discovery of cryptolepine's antihyperglycemic properties. As part of a medicinal chemistry program designed to optimize natural product lead structures originating from our ethnobotanical and ethnomedical field research, a series of substituted and heterosubstituted cryptolepine analogues was synthesized. Antihyperglycemic activity was measured in vitro and in an NIDDM mouse model to generate the first structure-bioactivity study about the cryptolepine nucleus.
Bierer
D E
DE
Shaman Pharmaceuticals, Inc., 213 East Grand Avenue, South San Francisco, California 94080, USA. dbierer@shaman.com
Dubenko
L G
LG
Zhang
P
P
Lu
Q
Q
Imbach
P A
PA
Garofalo
A W
AW
Phuan
P W
PW
Fort
D M
DM
Litvak
J
J
Gerber
R E
RE
Sloan
B
B
Luo
J
J
Cooper
R
R
Reaven
G M
GM
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D026121:Indole Alkaloids; D007211:Indoles; D051379:Mice; D008820:Mice, Obese; D010946:Plants, Medicinal / Q000737:chemistry*; D011804:Quinolines; D013329:Structure-Activity Relationship
D000470:Alkaloids; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; C024015:cryptolepine; D005947:Glucose