Antihyperglycemic sesquiterpenes from Psacalium decompositum.
Psacalium decompositum was investigated for antihyperglycemic compounds using diabetic ob/ob mice as a model for type 2 diabetes. In vivo bioassay-guided fractionation of an aqueous extract from the roots of P. decompositum led to the isolation of two new eremophilanolides, 3-hydroxycacalolide (1a) and epi-3-hydroxycacalolide (1b). A 1:1 mixture of 1a/1b exhibited antihyperglycemic activity when tested at 1.09 mmol/kg in ob/ob mice. The known furanoeremophilanes, cacalone (2a) and epicacalone (2b), were also isolated from the aqueous extract and were inactive. The known furanoeremophilane, cacalol (3), was isolated from a CH2Cl2 extract of P. decompositum roots and possessed antihyperglycemic activity. The relative stereochemistry in 1a and 1b was assigned 3R,5S and 3S,5S, respectively, based on ROESY data, 3J H-H values, and molecular mechanics calculations. Complete 13C and 1H NMR chemical shifts were assigned for 1a, 1b, 2a, 2b, and 3, and several revisions in 13C NMR assignments for 2a and 3 were made. Results from the conformational analysis of 1a, 1b, 2a, and 2b indicate that each compound exists in one major conformation in solution with H3-12 in a pseudoaxial position.
Inman
W D
WD
Shaman Pharmaceuticals Inc., 213 E. Grand Avenue, South San Francisco, California 94080, USA. winman@promega.com
Luo
J
J
Jolad
S D
SD
King
S R
SR
Cooper
R
R
D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004435:Eating / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008968:Molecular Conformation; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D012717:Sesquiterpenes