Description

ABSTRACT

The incidence of obesity along with its comorbidities are increasing markedly so much so that the term diabesity got coined. Hence the need of trying to treat the two conditions together. We have been reviewing how to get a better antiobesity drug helping in medical treatment that is preferable over the more expensive bariatric surgery (BS). Here we have further extended our previous publications on utilizing BAT/WAT As targets for introducing antiobesity therpy. In view of brown adipose tissue (BAT) hardly present in adult human beings the importance of beiging was highlighted earlier. Hence the accidental discovery of Mirabegron that has been used in OAB for long was detected to be a special β3 adrenergic receptor agonist having actions besides bladder on Adipose tissue (AT) lipolysis and beiging of white adipose tissue (WAT) along with increasing uncoupling protein 1 (UCP1) induction in WAT helped in trying to use it as the treatment of patients having diabesity in preference to BS. The only problem is recent some doubts that have arisen regarding safety profile of Mirabegron with upper airway angioedema along with rise in BP and prolongation of QT c interval on ECG, newer compounds are being studied on the basis of Comparative molecular field analysis (CoMFA) and Comparative molecular similarity index analysis (CoMSIA) studies and formation of contour maps. On the basis of quantitative structure – activity relationship (QSAR) 41 Aryloxy Propanol-Amine Agonists in a serial basis, were evaluated and validated certain drugs having antiobesity andantidiabetic effects for further evaluation for developing newer β3 adrenergic receptor agonists to replace Mirabegron.

Keywords: β3 adrenergic receptor agonist, Mirabegron, WAT Beiging, CoMFA, CoMSIA, UCP1