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  • Discovery of Natural Product Derived Labdane Appended Triazoles as Potent Pancreatic Lipase Inhibitors

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.

Pictorial Abstract