Ernesto Daniel Guevara Avendaño
Escuela Superior de Medicina del Instituto Politécnico Nacional
Mexico
Title: Evaluation of a series of phenylethylamine derivatives as β3-adrenoceptor agonist on the treatment of obesity
Biography
Biography: Ernesto Daniel Guevara Avendaño
Abstract
Obesity is a chronic disease associated with the increase in morbility of diabetes, hypertension, metabolic syndrome and cancer. Current drugs used in therapy stimulate the central nervous system and can cause unwanted sympathomimetic effect that may limit the use of these, here is the importance of research for new drugs with better defined target such is the case β3-adrenoceptor (β3AR). The purpose of studying β3AR is its participation in thermogenesis and lipolysis. The aim of the present work was to develop a series of ligands with higher affinity for the β3AR and characterize their activity in an in vitro and in vivo model. The in silico results suggest that the best molecules were IsF6S-15, IsF8R-15, IsF8S-15 and IsF9-15 satisfying the Lipinski's rules of 5. The molecule IsF1-15 was synthesized and characterized by NMR, IR and Mass spectrometry, then was tested in an in vivo model of obesity with male C57BL/6 mice. In vivo experiments showed that molecule IsF-15 have an significant effect on the decrease in weight (p<0.05), very similar to the reference, clobenzorex, which is currently used in México, other parameter that was modified was the triglycerides levels that had a significant decrease even more than clobenzorex. The glucose levels were not modified compared with the hyper control, this suggests that IsF-15 do not have significant effect on glucose and also cholesterol levels were similar to the control group. These results lead us to continue the research for phenylethylamine derivatives and their effect on β3AR on obesity therapy.