Identification of tanshinone IIA as a natural monoacylglycerol lipase inhibitor by combined in silico and in vitro approach

Abstract

Monoacylglycerol lipase (MAGL) was proposed as a novel target for the treatment of Alzheimer's disease (AD). In this paper, in silico screening of a focused library was implemented to dock natural products against MAGL to evaluate the calculated binding affinities of ligands with the receptor. Five hits were experimentally tested to determine their inhibitory effects on MAGL in vitro. Finally, tanshinone IIA (1) was successfully identified as a natural MAGL inhibitor in a concentration dependent manner with an IC₅₀ value of 48 μM. Considering being used as long-term treatment of cardiovascular diseases in China, tanshinone IIA has the potential to be developed as a good candidate for the treatment of AD and other MAGL-associated diseases.