Diamidines as Antibacterial Compounds

Wien, R.; Harrison, Jo; Freeman, W. A.

doi:10.1111/j.1476-5381.1948.tb00377.x

Cited by 12 publications

(7 citation statements)

References 8 publications

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“…A similar latency period in the antibacterial action of diamidines, was attributed to cellular penetration time (8). The prolonged S ânciif.z/Ercoli latency period (up to 48 h) in the advanced infection, besides a larger absolute number of more resistant organisms in an increased popula tion, depends probably also on sensitivity variations in the different reproductive phases of the parasite.…”

Section: Discussionmentioning

confidence: 80%

Activity of p-Biguanido-acetophenone-guanylhydrazone in Trypanosoma Equiperdum Infection

Sánchez¹,

Ercoli²

1965

Chemotherapy

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Section: Discussionmentioning

confidence: 80%

Activity of p-Biguanido-acetophenone-guanylhydrazone in Trypanosoma Equiperdum Infection

Sánchez¹,

Ercoli²

1965

Chemotherapy

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“…The cationic nature of these compounds has led to an explanation of their mode of action on the basis of competition with hydrogen ions for vital enzyme positions (Browning, Gulbransen, and Kennaway, 1919;Elson, 1945;Albert et al, 1945;Massart et al, 1947b). On the basis of the observed inhibitions of respiration by acridines (Silverman, Ceithaml, Taliaferro, and Evans, 1944;Ferguson and Thorne, 1946;Massart et al, 1947a;Deley, Peeters, and Massart, 1947;Marshall, 1948a) and by diamidines (Bernheim, 1943;Marshall, 1948b;Wien, Harrison, and Freeman, 1948), the negatively charged enzyme protein for which the drug cation and hydrogen ions compete is probably the dissociating acidic group of a respiratory enzyme. Quastel and Wheatley (1931) have suggested that the dehydrogenase system is primarily of an acidic nature on the basis that basic dyes inhibited and the acidic dyes did not inhibit the dehydrogenase activity.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic Studies on the Mechanism of the Resistance of Pneumococcus to Drugs

Sevag

Gots

1948

J Bacteriol

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In the preceding study (Gots and Sevag, 1948) it was shown that pneumococci made resistant to various drugs frequently possessed diminished dehydrogenase activities. It was suggested that the decreased dehydrogenase activity of the particular resistant organisms was a manifestation of a deficiency of susceptible sites, i.e., the resistant organisms depended on nonsusceptible metabolic sites for the maintenance of their physiological activities. The effect of the drugs on the dehydrogenase activity in the presence of the various substrates was therefore investigated to obtain information concerning these questions and to characterize certain of the enzymes involved in the production of the observed phenomena. Inhibition of Dehydrogenase Activity Methods and results. For the determination of the methylene-blue-reducing ability of the organisms a refinement of the technique used by Schnabel (1920) was used. This was substituted for the conventional Thunberg method, previously used, in order to facilitate the performance of simultaneous experiments with several substrates and varying concentrations of drugs, organisms, and other additions. Since some experiments involved 100 or more combinations, the use of Thunberg tubes would have been prohibitive. The technique, in effect, is a microadaption with some experiments being conducted with as little as 0.05 mg of organisms. The results obtained by this method are qualitatively, but not quantitatively, comparable to those obtained by the Thunberg technique. The bacterial suspension and the reagents used were prepared as previously described (Gots and Sevag, 1948). Using small serological tubes (10-by-100mm), the system consisted of 0.05 ml of methylene blue (0.001 M in M/20 phosphate buffer at pH 7.6), 0.1 ml of substrate, 0.1 ml of drug, bacterial suspension (0.1 mg per 0.1 ml), and M/20 phosphate buffer (pH 7.6) to give a total of 1 ml. The bacterial suspension was added last, the contents were immediately mixed, and 1 ml of melted petrolatum was carefully layered over the mixture. The tubes were then placed in a water bath at 37 C and the time in minutes required for 100 per cent reduction of the methylene blue was recorded. I The investigation was begun under a grant from the Josiah Macy, Jr. Foundation.

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“…66 Acquired resistance of S. aureus to propamidine and of S. pyogenes to dibromopropamidine have been demonstrated. 67,68 In each case, there was cross-resistance to other diamidines but not to penicillin or PF.…”

Section: Other Antibacterial Agentsmentioning

confidence: 97%