Phenyl acetate inhibition

Figure 10, Phenyl acetate inhibition of carboxypeptidase A-catalyzed hydrolysis of peptide, Dns-(Gly)g-i.-Phe, 1 X and the ester, Dns-(Gly)3-L.-0Phe, 4 X iO M (57), Enzyme concentrations were 5 X iO" and 4 X IO" M for ester and peptide hydrolysis, respectively (48, 57). Assays were performed in the absence (dashed Une) and presence (solid line) of 1 X phenyl acetate, 0Ac, at 25°C and...

At the start of this section the cleavage of meta- and para-substituted phenyl acetates by a- and )S-CD was discussed in detail and a variety of evidence was cited that is consistent with the mechanisms A and B, in Scheme 2. Further support for the view that para-substituents tend to force the phenyl group out of the cavity (Scheme 2B) comes from the different effects that neutral additives (potential inhibitors) have on the cleavage of m- and p-nitrophenyl acetate (mNPA and pNPA). In brief, species which bind to CDs, and inhibit the reaction of mNPA, do not necessarily inhibit that of pNPA (Tee and Hoeven, 1989 Tee et al., 1993b). 

We must stress that organo-phosphorus compounds are not specific inhibitors for the cholinesterases, but are rather inhibitors for enzymes possessing carboxylic esterase activity. All the enzymes mentioned below will hydrolyse carboxylic esters. However, not all esterases are inhibited, for example, A-esterase which hydrolyses phenyl acetate is not inhibited by organo-phosphorus compounds. 

Haagen, L., and A. Brock. 1992. A new automated method for phenotyping arylesterase (EC 3.1.1.2) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate. Eur J Clin Chem Clin Biochem 30 391. 

Davidson and co-workers568-571 found that benzene reacts withPd(OAc)2 in acetic acid at 100°C to give roughly equal amounts of biphenyl and phenyl acetate. The reaction time was reduced from 16 hr to 5 min at 100°C in the presence of perchloric acid,568 and the yield of biphenyl was higher. Formation of phenyl acetate was also inhibited in the presence of oxygen.571 These authors concluded that oxidative coupling proceeds via an unstable o-bonded arylpalladium complex, which rapidly decomposes to biaryls and Pd(I), that is,... 

Ram Z, Samid D, Walbridge S, Oshiro E, Viola J, Tao-cheng J-H, Shack S, Thibault A, Meyers C, Oldfield E (1994) Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenyl acetate. Cancer Res 54 2923-2927. 

Diclofenac is an NSAID with anti-inflammatory, analgesic, and antipyretic activity. It is an amino-phenyl-acetic acid derivative that inhibits prostaglandin biosynthesis to produce analgesic, antipyretic, and anti-inflammatory activity secondary to its nonselec-tive inhibition of the cyclooxygenase (COX) isoenzymes, COX-1 and COX-2. It lies approximately in the middle of the COX-l/COX-2 inhibitory spectrum. Uniquely among NSAIDs, diclofenac opens KCNQ2/3 potassium channels and may inhibit sensory neuronal depolarization. Please refer to the oral diclofenac chapter for additional information. 

De la Mare et al.260 measured the rates of chlorination of biphenyl, a wide range of its methyl derivatives, and anisole in acetic acid at 25 °C. Second-order rate coefficients (104 2) were biphenyl (6.40), 2-methylbiphenyl (3.20), 3-methyl-biphenyl (820), 4-methylbiphenyl (30.0), 2.2 -dimethylbiphenyl (4.40), 3.3 -dimethylbiphenyl (2,630), 4,4 -dimethylbiphenyl (70.0), 2,6 -dimethylbiphenyl (1,130), 3,4,3, 4 -tetramethylbiphenyl (19,300), anisole (12.5 x 104), and these results showed very clearly the effect of steric inhibition of resonance between the phenyl rings through the presence of ortho methyl groups260. Similar (but rather more emphatic) results were obtained262 in chlorination of the /-butyl derivatives for which the corresponding rate coefficients were 2-/-butylbiphenyl (1.0) 4-/-butylbiphenyl (25.7), 2,2 -di-/-butylbiphenyl (1.8), 4,4 -di-/-butylbiphenyl (70.0). 

Complexation with caffeine and theophylline-7-acetate depresses the rate of alkaline hydrolysis of substituted phenyl benzoates and is consistent with the formation of molecular complexes with 1 1 stoichiometry between the hosts and esters stacking of the xanthines is excluded as an explanation in the range of concentrations studied. Inhibition of hydrolysis is attributed to repulsion of the hydroxide ion from the host-ester complex by the extra hydrophobicity engendered by the xanthine host, as well as by the weaker binding of the transition state to the host compared with that in the host-ester complex. ... 

Fig. 4. Relationship between fluoride concentration and enzyme inhibition. Reaction mixtures contained in addition to substrate and fluoride, 0.1 M acetate, and 40-fold purified enzyme (in 0.01% gelatin), all at pH 5.5 in a 1.0-ml reaction volume. Points designated by triangles and plus symbols (+) are calculated from theory. Curve 1 /3-Glycerol-PO (13M). Curve 2 Yeast adenylic acid (0.044M). Curve 3 Phenyl-PO (0.14 M). From Reiner et al. (40).

Acetate buffer, pH 5 phenyl phosphate substrate liberated phosphate determined after 30 min at 37°. The figures represent the average percentage of activation (+) or inhibition (—) effected in several experiments. c D-(+)-Tartrate. 

In the case of atorvastatin, a lH-pyrrole ring system was selected [3], The synthetic 2-(4-fluoro-phenyl)-5-isopropyl derivative (Fig. 4.5) inhibited [uC]-acetate conversion to cholesterol in a crude rat liver homogenate. A optimization of its 3,4-disubstituted analogues resulted in atorvastatin. 

---