Discovery of Natural Product Derived Labdane Appended Triazoles as Potent Pancreatic Lipase Inhibitors
Renjitha Jalaja, Shyni Gangadharan Leela, Praveen Kumar Valmiki, Chettiyan Thodi F Salfeena, Kizhakkan T Ashitha, Venkata Rao D Krishna Rao, Mangalam S Nair, Raghu Kozhiparambil Gopalan* and Sasidhar Balappa Somappa*
Obesity contributes to the genesis of many metabolic disorders including dyslipidemia, coronary heart disease (CHD), nonalcoholic fatty liver, type 2 diabetes etc. Pancreatic lipase plays a vital role in food fat digestion and absorption. There-fore to control obesity, inhibition of pancreatic lipase is the active therapy. Thus, a novel natural product derived labdane appended triazoles with pancreatic lipase inhibition potential was designed and synthesized. Among these hybrids, two compounds exhibited excellent inhibitory activity (IC50 0.75 ± 0.02 ?M and 0.77 ± 0.01 ?M), slightly better than that of the positive control Orlistat (IC50 0.8 ± 0.03 ?M). Interestingly none of the compounds showed cytotoxicity (Hep G2) in the concentration ranging from 0.5-100 ?M. Overall results reveal potential of labdane appended triazoles as anti-obesity agents.
ACS Med. Chem. Lett., 2018, 9 (7), 662–666.