| Abstract
| - A novel class of potent human gastric lipase inhibitors, bis-2-oxo amide triacylglycerol analogues,was developed. These analogues of the natural substrate of lipases were prepared starting from1,3-diaminopropan-2-ol. They were designed to contain the 2-oxo amide functionality in place ofthe scissile ester bond at the sn-1 and sn-3 position, while the ester bond at the sn-2 position waseither maintained or replaced by an ether bond. The derivatives synthesized were tested for theirability to form stable monomolecular films at the air/water interface by recording their surfacepressure/molecular area compression isotherms. The inhibition of human pancreatic and gastriclipases by the bis-2-oxo amides was studied using the monolayer technique with mixed films of1,2-dicaprin containing variable proportions of each inhibitor. The nature of the functional group(ester or ether), as well as the chain length, at the sn-2 position influenced the potency of theinhibition. Among the compounds tested, 2-[(2-oxohexadecanoyl)amino]-1-[[(2-oxohexadecanoyl)amino]methyl]ethyl decanoate was the most potent inhibitor, causing a 50% decrease in HPL andHGL activities at 0.076 and 0.020 surface molar fractions, respectively.
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