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Synthesis of 2‐Oxo Amide Triacylglycerol Analogues and Study of Their Inhibition Effect on Pancreatic and Gastric Lipases
Author(s) -
Kokotos George,
Verger Robert,
Chiou Antonia
Publication year - 2000
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20001117)6:22<4211::aid-chem4211>3.0.co;2-#
Subject(s) - pancreatic lipase , amide , chemistry , biochemistry , lipase , stereochemistry , enzyme
A general method for the synthesis of chiral 2‐oxo amide triacylglycerol analogues, from ( R )‐ or ( S )‐3‐aminopropane‐1,2‐diol, was developed. These novel inhibitors of digestive lipases are analogues of the triacylglycerol molecule, a natural substrate of lipases, and they were designed to contain the 2‐oxo amide functionality in place of the scissile ester bond at the sn ‐1 or sn ‐3 position and nonhydrolysable ether bonds instead of ester bonds at the other two remaining positions. The 2‐oxo amide derivatives synthesised 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 porcine pancreatic and human gastric lipases by the 2‐oxo amides was studied by means of the monolayer technique with mixed films of 1,2‐dicaprin and with variable proportions of each inhibitor. The α 50 values of these triacylglycerol analogues for PPL and HGL varied between 4.4 to 7.0 % and 5.6 to 15.9 %, respectively. The chirality at the sn ‐2 position of 2‐oxo amide triacylglycerol analogues affected the α 50 value for HGL, but not for PPL.