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 alpha-position of each oleic acid residue were potent inhibitors; this caused a 50% decrease in HPL activity at 0.003 molar fraction.
Constantinou-Kokotou
Violetta
V
Chemical Laboratories, Agricultural University, of Athens, Iera Odos 75, Athens 11855, Greece. vikon@aua.gr
Magrioti
Victoria
V
Verger
Robert
R
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008049:Lipase / Q000037:antagonists & inhibitors*; D008567:Membranes, Artificial; D013499:Surface Properties; D014280:Triglycerides / Q000138:chemical synthesis / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D008567:Membranes, Artificial; D014280:Triglycerides; D008049:Lipase