title: Polyphenol fatty acid esters as serine protease inhibitors: a quantum-chemical QSAR analysis.
abstract: We investigated the ability of polyphenol fatty acid esters to inhibit the activity of serine proteases trypsin, thrombin, elastase and urokinase. Potent protease inhibition in micromolar range was displayed by rutin and rutin derivatives esterified with medium and long chain, mono- and polyunsaturated fatty acids (1e-m), followed by phloridzin and esculin esters with medium and long fatty acid chain length (2a-d, 3a-d), while unmodified compounds showed only little or no effect. QSAR study of the compounds tested provided the most significant parameters for individual inhibition activities, i.e. number of hydrogen bond donors for urokinase, molecular volume for thrombin, and solvation energy for elastase. According to the statistical analysis, the action of elastase inhibitors is opposed to those of urokinase and thrombin. Cluster analysis showed two groups of compounds: original polyphenols together with rutin esters with short fatty acid chain length and rutin esters with long fatty acid chain length.
authors: Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia. janaviskupicova@gmail.com
authors: Jana
authors: J
authors: Viskupicova
authors: Martina
authors: M
authors: Danihelova
authors: Magdalena
authors: M
authors: Majekova
authors: Tibor
authors: T
authors: Liptaj
authors: Ernest
authors: E
authors: Sturdik
mesh_terms: D000818:Animals; D002175:Candida / Q000737:chemistry / Q000201:enzymology; D002417:Cattle; D004929:Esculin / Q000737:chemistry; D004952:Esters; D005227:Fatty Acids / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D008049:Lipase / Q000737:chemistry; D062105:Molecular Docking Simulation; D010179:Pancreas / Q000737:chemistry / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010695:Phlorhizin / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory; D012431:Rutin / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D013379:Substrate Specificity; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014357:Trypsin / Q000737:chemistry*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
chemical_list: D004952:Esters; D005227:Fatty Acids; D005656:Fungal Proteins; D015842:Serine Proteinase Inhibitors; D004929:Esculin; D012431:Rutin; D010695:Phlorhizin; D008049:Lipase; C431349:lipase B, Candida antarctica; D010196:Pancreatic Elastase; D014357:Trypsin; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator