Ethnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities.
Using an ethnobotanical approach in combination with in vivo-guided fractionation as a means for lead discovery, cryptolepine was isolated as an antihyperglycemic component of Cryptolepis sanguinolenta. Two syntheses of cryptolepine, including an unambiguous synthesis, are reported. The hydroiodide, hydrochloride, and hydrotrifluoromethanesulfonate (hydrotriflate) salts of cryptolepine were synthesized, and a comparison of their spectral properties and their in vitro activities in a 3T3-L1 glucose transport assay is made. Cryptolepine and its salt forms lower blood glucose in rodent models of type II diabetes. While a number of bioactivities have been reported for cryptolepine, this is the first report that cryptolepine possesses antihyperglycemic properties.
Bierer
D E
DE
Shaman Pharmaceuticals, Inc., South San Francisco, California 94080, USA.
Fort
D M
DM
Mendez
C D
CD
Luo
J
J
Imbach
P A
PA
Dubenko
L G
LG
Jolad
S D
SD
Gerber
R E
RE
Litvak
J
J
Lu
Q
Q
Zhang
P
P
Reed
M J
MJ
Waldeck
N
N
Bruening
R C
RC
Noamesi
B K
BK
Hector
R F
RF
Carlson
T J
TJ
King
S R
SR
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005632:Fructose / Q000008:administration & dosage; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D007211:Indoles; D008297:Male; D051379:Mice; D008820:Mice, Obese; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D026121:Indole Alkaloids; D007211:Indoles; D010936:Plant Extracts; D011804:Quinolines; D005632:Fructose; C024015:cryptolepine; D005947:Glucose