Relation between lipophilicity of alkyl gallates and antifungal activity against yeasts and filamentous fungi

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 6; pp. 1793 - 1796
• Main Authors: Leal, P.C., Mascarello, A., Derita, M., Zuljan, F., Nunes, R.J., Zacchino, S., Yunes, R.A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-03-2009; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Arthrodermataceae - metabolism; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Drug Design; Drug Evaluation, Preclinical; Ergosterol - chemistry; Fungi - drug effects; Gallates; Gallic Acid - analogs & derivatives; Gallic Acid - chemistry; Lipophilicity; Medical sciences; Microbial Sensitivity Tests; Microsporum - metabolism; Microsporum gypseum; Molecular Structure; Pharmacology. Drug treatments; Structure-Activity Relationship; Gallates; Antifungal activity; Lipophilicity; Fungi; Antifungal agent; Yeast; Structure activity relation; Property structure relationship; Chemical synthesis; In vitro; Biological activity; Physicochemical properties
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.01.061

When the log
P of each gallate was calculated and related to the different values of MIC against
Microsporum gypseum it was observed that hexyl, heptyl, octyl and nonyl gallates exhibit a significant positive deviation from the curve corresponding to a polynomial equation obtained for the other gallates. This suggests that these compounds have a further mode of action besides their hydrophobicity, possibly the inhibition of some enzyme involved in ergosterol biosynthesis.
The antifungal activity of a complete series of 15
n-alkyl gallates and six analogues acting against a representative panel of opportunistic pathogenic fungi was studied in order to analyze their role in: the importance of the fungi tested, the importance of the hydroxyls, the influence of the chain length and the hydrophobicity of the compounds. It was demonstrated that dermatophytes were the most susceptible species and that hydroxyls appear to be necessary but not sufficient for the activity. When the log
P of each gallate was calculated and related to the different values of MIC against
Microsporum gypseum it was observed that hexyl, heptyl, octyl and nonyl gallates exhibit a significant positive deviation from the curve corresponding to a polynomial equation obtained for the other gallates. This suggests that these compounds have a further mode of action besides their hydrophobicity, possibly the inhibition of some enzyme involved in ergosterol biosynthesis.