Potentiating groups, additive effects

The possession of surface activity per se may be an important faetor in the antibacterial action of a group of drugs, for example the eationie detergents. The addition of low concentrations of surface-active compounds may potentiate the biological effect of an antibacterial agent. Thus, phenols are often more aetive in the presence of soaps. 

The additive effect of potentiating groups in the corticoid series is aptly illustrated by the fact that dexamethasone (24-3), which includes a methyl group at 16, fluorine... 

Most peptidyl a,a-difluoroalkyl ketones are actually extended chains based on statone, rather than simple difluoromethyl ketones. The statone derivatives are based on pepstatin, which is an extremely potent peptide inhibitor of aspartic proteases. The difluoro derivatives of statone take advantage of both the electronegativity of fluorine and the potential for additional interactions between the protease and structures on the leaving group side of the inhibitor. 15 This dual nature is part of what makes a,a-difluoroalkyl ketones effective inhibitors of aspartyl proteases as well as serine proteases. There are three main methods of synthesizing peptidyl a,a-difluoroalkyl ketones (1) the Reformatsky reaction with peptide aldehydes (Section 15.1.4.2.1), (2) a modified Dakin-West reaction (Section 15.1.4.2.2), and (3) a Henry nitro-aldol condensation (Section 15.1.4.2.3). 

As Illustrated in Fig. 7, 3 yM CRF and 1 yM (-)Isoproterenol cause a 190 and 110% stimulation of adenylate cyclase activity In rat pars intermedia particulate fraction, respectively. An additive effect Is observed when both stimulatory agents are present. Dopamine (30 yM), on the other hand, has no significant effect alone. However, In the presence of GXP, the catecholamine causes a 40 to 60% Inhibition of adenylate cyclase activity stimulated by CRF, ISO or CRF + ISO. It can also be seen that while 0.3 mM GXP alone causes a 100% increase In basal adenylate cyclase activity, it leads to a marked potentiation of the effect of ISO and CRF on [ 2P] cyclic AMP accumulation. It should be noticed that In the absence of the guanyl nucleotide, dopamine has no Inhibitory effect on adenylate cyclase activity In any of the groups studied. 

Multiple-species risk for independent combined effects in terms of the potentially affected fraction of species can be assessed using models that are essentially the same as for the prediction of response-additive effects in single species. The underlying assumption in the application of a response addition model for compounds or groups of compounds with different modes of action is that correlation of species sensitivities to the different constituents of the mixture is again considered absent. The calculation... 

Subsequent to the synthesis of 5-carba-5-deaza- and 1-carba-1-deazariboflavin, the Merck group synthesized 1,5-dideazari-boflavin, XIV, with both redox-active nitrogens replaced by carbon (22). Some expected patterns of reactivity are observed. The reduction potential for two-electron reduction to the dihydro form, XV, has been estimated at —370 mV, an essentially additive effect from the two deazaflavins previously noted. This low value puts XIV out of the... 

Our research group has studied the effect of using platinum salts in the synthesis of mesoporous silica with a view to the preparation of Pt-supported silica solids [11], which possess a high catalytic potential. In addition, this methodology could be extended to the synthesis of other metals supported on alternative materials compatible with the sol-gel route. 

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