Synergism inhibitors

Clavulanic acid has only weak antibacterial activity, but is a potent irreversible inhibitor for many clinically important P-lactamases (10—14,57,58) including penases, and Richmond-Sykes types 11, 111, IV, V, VI ([Bacteroides). Type I Cephases are poorly inhibited. Clavulanic acid synergizes the activity of many penicillins and cephalosporins against resistant strains. The chemistry (59—63), microbiology (64,65), stmcture activity relationships (10,13,60—62,66), biosynthesis (67—69), and mechanism of action (6,26,27,67) have been reviewed. 

Molybdate is always used in conjunction with other anion inhibitors, not only to reduce the cost of the inhibitor program, but also because, through synergism, much-improved barrier films are produced when coupled with nitrite or silicate. 

Although azoles are commonly thought of as only yellow metal inhibitors, they are, in fact, used for corrosion inhibition in a wider range of metals such as steel and aluminum. They also are often incorporated in molybdate-based programs to both provide some synergism and reduce the level of molybdate required. Azoles also are employed in many types of organic-based formulations, where they improve the overall protection of steel and reduce the risk of corrosion of yellow metals due to the corrosive action of some common phosphonates. 

The effectiveness of various chemicals such as IH-benzotriazole, 2-methyl-benzotriazole, and 2-phenylbenzimidazole as a corrosion inhibitor for mild steel in 15% HCl was investigated by weight loss and electrochemical techniques [1547]. Among different azoles, 2-phenylbenzimidazole has shown the best performance. A synergism of iodide and 2-phenylbenzimidazole was observed. 

Preparation of Krebs-2 translation extracts Krebs-2 extracts are an ideal system to screen for compounds that inhibit translation because they faithfully recapitulate the cap dependency and the cap-poly(A) synergism associated with eukaryotic mRNA translation (Svitkin and Sonenberg, 2004), unlike standard rabbit reticulocyte lysates (RRL) (Borman et al., 2000). Furthermore, the translation of many types of IRESes is supported in Krebs-2 extracts. The use of commercially available translation competent extracts prepared from RRL, wheat germ, and E. coli is extremely useful in assessing selectivity of inhibitors identified in primary screens. 

For initiated oxidation, the inhibitory criterion could be defined as the ratio v0/v or (v0/ v — v/v0), where v0 and v are the rates of initiated oxidation in the absence and presence of the fixed concentration of an inhibitor, respectively. Another criterion could be defined as the ratio of the inhibition coefficient of the combined action of a few antioxidants / to the sum of the inhibition coefficients of individual antioxidants when the conditions of oxidation are fixed (fx = IfiXi where f, and x, are the inhibition coefficient and molar fraction of z th antioxidant terminating the chain). It should, however, be noted that synergism during initiated oxidation seldom takes place and is typical of autoxidation, where the main source of radicals is formed hydroperoxide. It is virtually impossible to measure the initial rate in the presence of inhibitors in such experiments. Hence, inhibitory effects of individual inhibitors and their mixtures are usually evaluated from the duration of retardation (induction period), which equals the span of time elapsed from the onset of experiment to the moment of consumption of a certain amount of oxygen or attainment of a certain, well-measurable rate of oxidation. Then three aforementioned cases of autoxidation response to inhibitors can be described by the following inequalities (r is the induction period of a mixture of antioxidants). 

Synergism of antioxidants was reviewed in the monographs [1-9]. The classification of binary mixtures of inhibitors is based on the mechanisms of action of particular inhibitors [10,11], One of the classification schemes is given in Ref. [11], If one takes into account the... 

Among methoxy-substituted yohimbine alkaloids, only 11-methoxy-a-yohim-bine (95) and 1 l-methoxy-3-epi-a-yohimbine (106) were tested for a-adrenergic activity, and they showed only weak a2-adrenoceptor blocking effect (347). On the other hand, venenatine (107) has reserpinelike activity and shows synergism with reserpine (109). Furthermore, alstovenine (96) displays monoamine oxidase inhibitor activity (348). 

The lytic enzyme systems, active against yeast cell walls, usually contain l,3-/ -glucanases, proteases, mannanases, chitinases, and 1,6-) -glucanases. The proportion of those enzyme activities, their action pattern, synergism, and dependence on inhibitors constitute the activity profile... 

Support for this is found in the substantially greater octopa-minomimetic activity of DCDM compared to chlordimeform (20) and the observation that mixed function oxidase inhibitors, e.g. piperonyl butoxide and sesamex, strongly antagonized the toxicity of chlordimeform to the southern cattle tick larvae and synergized the toxicity of DCDM (21). Therefore, chlordimeform may be considered to be a propesticide of DCDM. 

SUBSTRATE SYNERGISM SLOW TEMPERATURE-JUMP METHODS DEPOLYMERIZATION, END-WISE SLOW, TIGHT-BINDING INHIBITOR... 

DeBattista, C., Sofuoglu, M., and Schatzberg, A.F. (1998) Serotonergic synergism the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs. Biol Psychiatry 44 341—347. 

An alluring field of research is the mechanism of action of oxidation inhibitors. This research will undoubtedly yield in the near future a theory for inhibition of undesirable oxidation processes. The relatively stable free radicals observed on such inhibition display extremely interesting properties. Of great interest are the effects of synergism, of inhibitor mixtures, and of mixtures of inhibitors with catalysts. A strictly quantitative and elegant description of all these phenomena may be made within the scope of the chain theory for slow oxidation. 

Other synergistic antimicrobial combinations have been shown to be more effective than monotherapy with individual components. Trimethoprim-sulfamethoxazole has been successfully used for the treatment of bacterial infections and Pneumocystis jiroveci (carinii) pneumonia. 3-Lactamase inhibitors restore the activity of intrinsically active but hydrolyzable 3-lactams against organisms such as S aureus and Bacteroides fragilis. Three major mechanisms of antimicrobial synergism have been established ... 

Inhibition of enzymatic inactivation Enzymatic inactivation of 3-lactam antibiotics is a major mechanism of antibiotic resistance. Inhibition of 3-lactamase by 3-lactamase inhibitor drugs (eg, sulbactam) results in synergism. 

Synergism - a potentiation or prolongation which results in much greater than expected effects. This could involve competitive substrates for an enzyme or receptor, decreased excretion, displaced plasma protein binding, etc. The analgesic propoxyphene (Darvon ) slows down the excretion of ethanol and so increases the depressant effects of the alcohol. Recall the example given earlier of the monoamine oxidase inhibitors used as antidepressants and the tyramine-containing foods which could precipitate a hypertensive crisis. 

Dispositional interactions are those in which one chemical affects the disposition of the other, usually metabolism. Thus, one chemical may increase or inhibit the metabolism of another to change its toxicity. For example, 2,3-methylenedioxynaphthalene inhibits cytochrome P-450 and so markedly increases the toxicity of the insecticide carbaryl to flies (potentiation) (see chap. 5). Another example, which results in synergy, is the increased toxicity of the organophosphorus insecticide malathion (see chap. 5) when in combination with another organophosphorus insecticide, EPN. EPN blocks the detoxication of malathion. Many chemicals are either enzyme inhibitors or inducers and so can increase or decrease the toxicity of other chemicals either by synergism or potentiation (see chap. 5). 

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