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

Renjitha Jalaja; Shyni G Leela; Praveen K Valmiki; Chettiyan Thodi F Salfeena; Kizhakkan T Ashitha; Venkata Rao D Krishna Rao; Mangalam S Nair; Raghu K Gopalan; Sasidhar B Somappa

doi:10.1021/acsmedchemlett.8b00109

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

ACS Med Chem Lett. 2018 Jun 18;9(7):662-666. doi: 10.1021/acsmedchemlett.8b00109. eCollection 2018 Jul 12.

Authors

Renjitha Jalaja^{1

2}, Shyni G Leela³, Praveen K Valmiki^{1

2}, Chettiyan Thodi F Salfeena^{1

2}, Kizhakkan T Ashitha^{1

2}, Venkata Rao D Krishna Rao⁴, Mangalam S Nair¹, Raghu K Gopalan^{3

2}, Sasidhar B Somappa^{1

2}

Affiliations

¹ Chemical Sciences and Technology Division, CSIR - National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram - 695 019, Kerala, India.
² Academy of Scientific and Innovative Research (AcSIR), CSIR-NIIST, Thiruvananthapuram - 695 019, Kerala, India.
³ Agro-Processing and Technology Division, CSIR-NIIST, Thiruvananthapuram - 695 019, Kerala, India.
⁴ CSIR - Central Institute of Medicinal and Aromatic Plants, Research Centre, Bangalore - 560065, Karnataka, India.

Abstract

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. Therefore, to control obesity, inhibition of pancreatic lipase is the active therapy. Thus, novel natural product derived labdane appended triazoles with pancreatic lipase inhibition potential were designed and synthesized. Among these hybrids, 6b and 6f exhibited excellent inhibitory activity (IC₅₀ 0.75 ± 0.02 μM and 0.77 ± 0.01 μM), slightly better than that of the positive control Orlistat (IC₅₀ 0.8 ± 0.03 μM). Compounds 6c, 6e, and 6g-j inhibited the PL comparable to that of positive control. Interestingly none of the compounds showed cytotoxicity (Hep G2) in the concentration range from 0.5 to 100 μM. Overall results reveal the potential of labdane appended triazoles as antiobesity agents.