New potential nonsteroidal anti-inflammatory drugs with antileukotrienic effects: influence on model proteins with catalytic activity.
Unspecific and side effects caused by interaction with proteins belong to common problems of many structures synthesized as potential medicaments. Possible in vitro interactions with proteins of a group of phenylsulfonyl benzoic acid derivatives (VUFB 19363, 19369, 19370, 19371, and 19760) as new potential anti-inflammatory compounds with anti-leukotrienic activities were studied in the present work. Three purified enzymes were used as model proteins with catalytic activities: Pig heart aspartate aminotransferase (AST, EC 2.6.1.1), alanine aminotransferase (ALT, EC 2.6.1.2), and glutamate decarboxylase (GAD, EC 4.1.1.15) from E. coli. Catalytic activities during incubation of individual compounds (6 x 10(-5) M solution to 5 x 10(-2) M suspension) at 37 degrees C with enzymes served as criteria of stability and function of the proteins. No immediate influence of any compound studied on enzyme activities was found. Aminotransferase activities were not affected even during incubation up to 20 d. In the case of GAD, the compounds VUFB 19369, 19370, 19371, and 19760 had stabilizing influence on GAD activity during incubation at enzyme concentrations of 11.25 and 5.62 mg prot/l. The lack of an immediate effect of compounds and the stability of enzymes during incubation them are favorable and support the prospective of the compounds as potential drugs.
Netopilová
Miloslava
M
Department of Biochemical Sciences, Charles University, Prague, Faculty of Pharmacy, Hradec Králové, LN00B125. netopilo@faf.cuni.cz
Drsata
Jaroslav
J
Beránek
Martin
M
Palicka
Vladimír
V
D000410:Alanine Transaminase / Q000737:chemistry / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000737:chemistry / Q000187:drug effects; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis / Q000187:drug effects; D004347:Drug Interactions; D004798:Enzymes / Q000737:chemistry / Q000187:drug effects*; D004926:Escherichia coli / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000737:chemistry / Q000187:drug effects; D020024:Leukotriene Antagonists / Q000737:chemistry / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001565:Benzoates; D004798:Enzymes; D020024:Leukotriene Antagonists; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005968:Glutamate Decarboxylase