Anions Antibacterial action

Under acidic conditions, dehydration to an anhydrotetracycline [20154-34-1] (8), C22H22N20y, occurs under basic ones, ring C opens to an isotetracycline [3811-31-2] (9), C22H24N20g. The anhydrotetracyclines, such as (8), appear to exhibit a mode of antibacterial action, but it is unlike that of tetracycline (24). Epimerization (23,25,26) at C-4 occurs in a variety of solvents within the pH range 2—6, particularly in acetic acid (25). A number of anions (27) facihtate this reaction. The reverse process, from 4-epitetracycline [79-85-6] C22H24N20g, to tetracycline, is promoted by chelation with ions such as calcium and magnesium (28). 

Another instability leading to a dramatic decrease of antibacterial action, to which all clinically used tetracyclines are subject, is epimerization of the natural 4-a-dimethy-lamino group A to the p-epimer B (Eq. 6.11). Under acidic conditions a 1 2 equilibrium is established in solution within a day. This occurs in a variety of solvents, especially acetic acid. Anions also tend to support this process. Divalent ions that chelate tetracyclines, particularly Ca2+, facilitate the reversal of the epimerization from the epi to the natural isomer. 

Cationic and anionic antibacterials with other types of action... 

That sulfonamides act as the anion but penetrate into the bacterial cell as the neutral species was later confirmed by comparing their behaviour in (a) a cell-free folate-synthesizing preparation of E. coli and (b) the intact cells of E. coli. The antibacterial action was directly proportional to percentage ionized in (a) but became dependent on lipophilicity, as well, in (b) (Miller, Doukos and Seydel, 1972). 

Gillissen [104] finds that the antibacterial action of tyrothricin is influenced by the presence of solubilizers. Cationic surfactants have a synergistic effect (as mentioned above) on its activity against Gram-positive and Gram-negative bacteria, whereas polysorbate 80 inhibits its activity. It is thus important that these effects are borne in mind, and a compromise must be found between the stability and incompatibility characteristics of the solution and the activity of the product. The complexity of the situation is revealed by the fact that the activity of bacitracin is enhanced by the presence of cationic and non-ionic surfactants [106] but decreased by anionic agents. The effect of non-ionic surfactants on the bactericidal activity of tyrothricin has been measured [107]. Some results are shown in Table 6.11. 

P-Lactam antibiotics exert their antibacterial effects via acylation of a serine residue at the active site of the bacterial transpeptidases. Critical to this mechanism of action is a reactive P-lactam ring having a proximate anionic charge that is necessary for positioning the ring within the substrate binding cleft (24). 

Although the alkylphenols, the quaternary amines, and the polypeptide antibiotics are surface-active, this property alone cannot cause biological action (Luduena et al., 1955). Ordinary surface-active substances of the three charge-types (cationic, anionic, and neutral) are highly antibacterial, slightly anti-... 

In 1935 Domagk (40) discovered the powerful germicidal action of the quaternary ammonium salts, thus introducing the first important application of synthetic detergents to biological systems. In the last ten years reports too numerous to mention have revealed the antibacterial effects of both the cationic and anionic detergents (for reviews, see Dubos, 41, 42 Daniels, 36 and Valko, 147). 

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