Activity Inhibition

The esters of monofluorophosphoric acid are of great interest because of their cholinesterase inhibiting activity which causes them to be highly toxic nerve gases and also gives them medical activity (see Enzyme inhibitors). The most studied is the bis(l-methylethyl)ester of phosphorofluoridic acid also known as diisopropyl phosphorofluoridate [155-91 DFP (5), and as the ophthalmic ointment or solution Isoflurophate USP. It is used as a... 

Several natural products, eg, gymnemic acid [122168-40-5] and 2i2iphin [73667-51-3] have also shown sweet-inhibiting activities. These are not allowed for foods in the United States, however. 

Certain inorganic monovalent anions, similar in size to I, are also taken up by the thyroid gland and competitively inhibit active iodide transport with the following decreasing potencies ... 

Other Unusual P-Lactam Based Inhibitors. There are a number of other unusual p-lactams reported to have p-lactamase inhibition activity (191—194). In general these compounds are not very potent and are not irreversible inhibitors. Data are also very Umited. 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

In the discussion of benzylamines, we have met medicinal agents that owe their activity to some particular functionality almost without reference to the structure of the rest of the molecule. The hydrazine group is one such function in that it frequently confers monamine oxidase-inhibiting activity to molecules containing that group. Such agents frequently find use as antidepressants. Thus, reduction of the hydrazone of phenyl-acetaldehyde (84) affords the antidepressant phenelzine (85). Similar treatment of the derivative of phenylacetone (86) gives pheniprazine (87). ... 

Hydrazides of isonicotinic acid have been used as antidepressant agents by virtue of their monoamine oxidase-inhibiting activity the pyridine ring has been shown to be replaceable by an... 

Alkylation of the monobenzhydryl derivative of piperazine ( ) with the same alkylating agent gives oxatomide (59), after removal of the protecting group.This agent shows antihistaminic activity as well as some mediator release inhibiting activity, a... 

Carboxylic acid derivatives of heterocycles have proved a source of compounds that show the same allergic mediator release inhibiting activity as sodium cromoglycate. A number of these agents have been taken to the clinic for trial as antiallergic agents. 

The observation that a carboxyl derivative of a pyrimidinoquinol ine shows mediator release inhibiting activity is in consonance with the earlier generalization. Knoevenagel condensation of nitroaldehyde 138 with cyano-acetamide gives the product 139. Treatment with iron in... 

The earboxylie aeid derivative of an isomerie fused thienopyrimidine exhibits mediator release inhibiting activity. The apparently complex thiophene 126 can be obtained in a single step by... 

For a couple of years 0.25% Hg became the technical standard. It has to be pointed out that the mercury content of the metallic zinc has to be divided by a factor of roughly 10 to give the mercury content based on the total cell weight of an AA (LR-6) cell. These values are sometimes indicated on the cell labels. With decreasing amalgamation, other corrosion inhibitors had to take over the role of mercury. There are numerous papers and patents claiming corrosion-inhibiting activities of elements like A1, In, T1, Cd, Ga, Na, ... 

Cytokines. Figure 1 Inhibition of cytokine synthesis during activation of the specific immune system. The monoclonal antibodies Muromonab and Basiliximab are specific for the CD3 complex of the T-cell receptor, and for the IL-2 receptor on lymphocytes, respectively. Cyclosporin and Tacrolimus inhibit activation of cytoplasmic NF-AT, a transcription factor essential for activation of the IL-2 gene ( NFAT Family of Transcription Factors). Sirolimus interferes with mTOR signaling and inhibits IL-2 dependent proliferation. Red pharmaka, blue target proteins. 

STAT signaling occurs within minutes following activation but also underlies rapid deactivation by cytoplasmic phosphatases or antagonistic factors such as members of the SOCS-proteins themselves induced by activated STATs. Another group of proteins called PIAS (proteins that inhibit active STATs) inhibit binding of activated STATs to their target DNA sequences... 

Cimetidine, an H2 antagonist used therapeutically in patients with ulcers, inhibits activity of hepatic microsomal enzymes. When rats or mice were pretreated with cimetidine, dose-related lethality of methyl parathion was reduced, and cholinergic signs of toxicity were delayed. Simultaneous administration with methyl parathion did not reduce toxicity (Joshi and Thornburg 1986). 

Taylor JM, QuUty D, Banadyga L, Barry M (2006) The vaccinia virus protein FIL interacts with Bim and inhibits activation of the pro-apoptotic protein Bax. The Journal of biological chemistry 281 39728-39739... 

Tartrate is a most widely used inhibitor of prostatic acid phenylphosphatase activity. With this inhibitor Bonner and associates detected five cases of unsuspected carcinoma of the prostate in 221 hospital patients and clarified the diagnoses in another four patients (98). Nonetheless, the diagnostic specificity of an elevated 1-tartrate inhibited activity is not absolute, as Fishman et. al found it elevated in 48 of 1,190 males without cancer. Whitmore and associates also observed this activity to be elevated in 3 of 20 patients with uncomplicated nodular hyperplasia (102). Hill compared the total versus the "prostatic" serum activities in 20 patients with localized untreated carcinoma of the prostate and observed... 

Certain chemical substances have been known for many years to uncouple oxidation firm phosphorylation and to inhibit active transport, and for this reason they are named imcoupling agerrts. They are beheved to act by rendering the membrane permeable to protons hence short-circuiting the potential gradient or protonmotive force. 

The reason for this disappointing response is uncertain but may be due to desensitisation of the GABAa receptors, or the actual inhibition of GABA inhibitory neurons through somatic autoreceptors which could disrupt the precise timing of physiological inhibition. Activation of the GABAb receptor with baclofen has no... 

Tibaduiza, E.C. et al., Excentric cleavage products of beta-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1-mediated transcriptional activation, J. Nutr., 132, 1368, 2002. 

Xanthine oxidase (XO) is not only an important biological source of ROS but also the enzyme responsible for the formation of uric acid associated with gout leading to painful inflammation in the joints. The XO inhibition effect by the enzymatically synthesized poly(catechin) increased as an increasing concentration of catechin units, while the monomeric catechin showed almost negligible inhibition effect in the same concentration range. ° This markedly amplified XO inhibition activity of poly(catechin) was considered to be due to effective multivalent interaction between XO and the condensed catechin units in the poly (catechin). 

The PL-catechin conjugate showed greatly amplified concentration-dependent inhibition activity against bacterial collagenase (ChC) on the basis of the catechin unit, which is considered to be due to effective multivalent interaction between ChC and the catechin unit in the conjugate. The kinetic study suggests that this conjugate is a mixed-type inhibitor for ChC. Hyaluronidase is an enzyme which catalyzes hydrolysis of hyaluronic acid and is often involved in a number... 

A copper(II) complexes of 5-phenylazo-3-methoxy salicylidene thiosemicarbazone has been shown to have promising growth inhibition activity against P388 lymphocytic leukemia cells sensitive and resistant to adriamycin [196], The complex involves ON coordination of two deprotonated ligands and v(CS) is reported to be unaltered in intensity and position in the complex from its position in the spectrum of the ligand. Inhibition studies with the uncomplexed thiosemicarbazone indicating an important role for the copper(II). 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

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