Benzylguanidines and other galegine analogues inducing weight loss in mice.
Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.
Strathclyde Institute for Pharmacy and Biomedical Sciences and Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK. geoff.coxon@strath.ac.uk
Geoffrey D
GD
Coxon
Brian L
BL
Furman
Alan L
AL
Harvey
John
J
McTavish
Mark H
MH
Mooney
Mahmoud
M
Arastoo
Alan R
AR
Kennedy
Justice M
JM
Tettey
Roger D
RD
Waigh
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage; D006146:Guanidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008820:Mice, Obese; D008862:Microsomes, Liver / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects*
D019440:Anti-Obesity Agents; D001593:Benzyl Compounds; D004041:Dietary Fats; D006146:Guanidines; C117872:benzylguanidine; C074315:galegine