THE EFFECTS OF pH ON THE ANTIFUNGAL ACTIVITY OF FATTY ACIDS AND OTHER AGENTS*
PRELIMINARY REPORT
E. J. FOLEY, F. HERRMANN, M.D. AND S. W. LEE, PR.D. Certain fatty acids, some of which are components of normal sweat, have a strong antifungal action against pathogenic and nonpathogenic fungi.** It was reported by Marchionni et al. (la, b, c, d), Herrmann et a!. (2, 3, 5), Hoffman et al. (6), Rigler and Greathouse (7), that these acids are more active at low than at higher pH. These findings would indicate that the free acids are more effective than their salts. However, Peck and Rosenfeld (8) stated that sodium propionate and sodium undecylenate are more active than the respective acids, and the experiments of Hillegas and Camp (9) suggest that undecylenic acid is more active at pH 8 than at pH 5 or 6. The following experiments were undertaken to study further the effects of pH on certain antifungal agents.
EXPERIMENTAL SERIES I Technic Serial dilutions of the agents were made in equal parts of propylene glycol and water. One-tenth ml. of each dilution was mixed with 5 ml. of melted Sabouraud's agar, buffered at different pH with 20 vol. per cent of Mc Ilvaine's standard buffers, and agar slant8 prepared. The p11 figures as given on table 1 were determined electrometrically before inoculation. The tubes were inoculated with one drop of a suspension of Trichophyon gypseum (A.T.C.C. 9533) spores. Results While acetic, propionic, butyric, lactic, heptylic, caprylic, pelargonic, capric, undecylenic, para-aminobenzoic, and 2—4 dichiorophenoxy acetic acids, and tn- methyl cetyl animonium pentachiorphenate were studied, we here report only on the behavior of propionic, heptylic, caprylic, pelargonic, capric and Un- decylenic acid, and of trimethyl cetyl ammonium pentachiorphenate. These substances were chosen because they represent three different groups of anti- fungal agents. Propionic acid is a water-soluble fatty acid; capric, caprylic, heptylic, pelargonic and undecylenic acids are practically insoluble in water; and TCAP is an extremely fungicidal quaternary ammonium salt (8). The *Fromthe New York Skin & Cancer Unit, New York Post-Graduate Medical School and Hospital, Columbia University, and the Wallace Laboratories, mc, New Brunswick, New Jersey. Received for publication, July 4, 1946. **Amore detailed review of the pertinent literature will be presented in a future publi- cation. 1 2 THEJOURNAL OF INVESTIGATIVE DERMATOLOGY results are shown in one example on table 1. Suitable controls with the solvent liquid alone showed no inhibition of growth at any of the selected pH values. TABLE 1 Effect of pH in agar medium on fun gistatic properties of agents dissolved in equal parts of propylene glycol and water
SAB0VRAVD'S AGAR BtTTERED AT pH 01: ANTIPUNGAL AGENT 5.0 5.6 6.0 7.0 8.0
Propionic acid 0.33* 0.33 1.0 2.0 Heptylic acid 0.066 0.10 0.50 Caprylic acid 0.02 0.05 0.2 Pelargonic acid 0.012 0.066 0.4 Capric acid 0.01 0.04 0.066 Undecylenic acid 0.01 0.025 0.1 0.50 Trimethyl cetylammonium pentachior- phenate 0.012 0.03 0.07 0.12 * These figures give the minimal concentration completely inhibiting growth of T. Gypsum, expressed in mg. of agent per Gm. of medium.
EXPERIMENTAL SERIES II Technic Inthisseries, the fun gicidal action of capric, caprylic, heptylie, pelargonic and unde- cylenic acids was ascertained in broth at various pH. Tubes containing 0.5% of the acids, in 5 ml. of equal parts of water and propylene glycol, buffered at pH 5, 6, 7and8, were inoculated with Trichophyton gypseum spores according to a modification of the quantitative method of Emmons (10). Loop transfers were made into 10 ml. of broth (p11 7.0—buffer) at intervals of 10, 20, and 30 minutes. Results The presence or absence of growth, recorded after 2 weeks, was as follows: (1) Heptylic and caprylic acids did not kill the spores at any pH within the 30-minute exposure. (2) Undecylenic acid killed within 10 minutes at pH 5, and within 20 minutes at pH 6.(3) Pelargonic and capric acids were fungicidal within 10 minutes at pH 5. Capric acid was fungicidal within 30 minutes also at pH 6. (4) No fungicidal effect was observed with any of the acids at pH 7 and 8. (5) TCAP in 0.1% concentration was fungicidal within 10 minutes at all four pH levels.
SUMMARY Under the experimental conditions described, a series of fatty acids as well as trimethyl cetyl ammonium pentachiorphenate (TCAP) proved to be more antifungal at pH 5 than at higher p11 levels. REFERENCES
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NOTICE In accordance with the authorization granted him at the seventh annual meeting, the Chairman of the Editorial Board has appointed Dr. Naomi M. Kanof of Washington, D. C. as an additional member of the Editorial Board.