Acetamidoquinone and acetamidohydroxy derivatives as inhibitors for both dihydroxyacetamido epoxidase and dehydrogenase.
A series of monohydroxy and dihydroxyacetanilides, acetamidoquinones and bromoacetamidoquinones have been synthesised and tested as substrates and/or inhibitors of highly purified dihydroxyacetamido epoxidase (DHAE) and dihydroxy acetamido dehydrogenase (DHADH) from Streptomyces LL-C10337. None was found to act as substrates but many selectively inhibit the enzymes. Kinetic analysis has shown that all the compounds act as reversible competitive inhibitors with respect to the substrates 2,5-dihydroxyacetanilide and 2,3-epoxy-1,4-benzoquinone-5-acetanilide. Monohydroxy acetanilides showed weak inhibition to these enzymes compared to the dihydroxy derivatives while the more powerful inhibitors were the benzoquinoneacetanilide and its 5-bromo equivalent.
Whiteley
Chris G
CG
Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa. c.whiteley@ru.ac.za
D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000083:Acetanilides / Q000138:chemical synthesis / Q000494:pharmacology; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D007700:Kinetics; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013302:Streptomyces / Q000201:enzymology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000081:Acetamides; D000083:Acetanilides; D004791:Enzyme Inhibitors; D011809:Quinones; D000429:Alcohol Oxidoreductases; C472994:dihydroxyacetamido dehydrogenase; D010105:Oxygenases; C472993:dihydroxyacetanilide epoxidase