๐”– Bobbio Scriptorium
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The chemotherapy of phenanthridine compounds

โœ Scribed by Walls, L. P.


Book ID
102888484
Publisher
Wiley (John Wiley & Sons)
Year
1947
Weight
672 KB
Volume
66
Category
Article
ISSN
0368-4075

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โœฆ Synopsis


It is significant that the constant b remains unchanged for all the alkyl 4-hydroxybenzoates tested. This constant expresses the change of inhibition with conantration, and the fact that this is the same for the homologous series suggests a similar mechanism of action associated with the 4-hydroxybenzoate grouping. Work to be published in detail later shows that th; 6 value for the series can be altered by changes in the " head grouping ; that is, by alkylation of the hydroxyl group, or by substitution in the nucleus ortho-to the hydroxyl group. Phenol, lacking the para-carboxyl group, has a different b value -0.9, and this general value is also found in a para-substituted alkyl phenol, such as ptett.-amyl phenol. 4-Hydroxybenzoic acid itself, although less effective than its methyl ester, shows the same b relationship over the comparable portion of its dosage/ response curve (Fig. 5). The constancy in the relationship of b between esters of 4-hydroxybenzoic acid suggests a possible function, involving both polar groups associated with the aromatic nucleus, in relation to specific sites on the organism; the b value reflecting the decreasing relative availability of further activity centres with increased dose.

The constant a, related to the experimentally determined inhibitory index I, is a measure of the effect on inhibition of a change in the size or shape of the ester grouping. The ' I tail's " function is then interpretable as firstly, anchoring by increased adsorbability, and secondly, increasing penetration to an active a n t r e by its lipophilic properties. The variable reactions of the three moulds to chain length, as determined by the a (= I) value, would seem to reflect specific chemical and physical relationship between the alkyl " tail l' and some, possibly lipid, phase of the organism concerned. The mode of action, therefore, including entry and action at an active centre, would probably depend upon both "head" and "tail" groupings present (cf. %deal1&).

Only physico-themical aspects of inhibition have been discussed, the mode of action of the compounds on the biological system being at present unknown.


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