Sterically Hindered Triacylglycerol Analogues as Potent Inhibitors of Human Digestive Lipases

A novel class of inhibitors of human digestive lipases have been developed. Various sterically hindered triacylglycerols based on 2‐methyl‐ and 2‐butylglycerol, and/or 2‐methyl fatty acids were synthesized. The triacylglycerol analogues were tested for their ability to form stable monomolecular films at the air/water interface by recording their surface‐pressure/molecular‐area compression isotherms. The inhibition of human pancreatic and gastric lipases by the sterically hindered triacylglycerol analogues was studied by using the monolayer technique with mixed films of 1,2‐dicaprin, which contained variable proportions of each inhibitor. Triolein analogues that contain a butyl group at the 2‐position of the glycerol backbone or methyl groups both at the 2‐position of glycerol, and the α‐position of each oleic acid residue were potent inhibitors; this caused a 50 % decrease in HPL activity at 0.003 molar fraction.