Bioorganic & Medicinal Chemistry Letters 11 (2001) 347±350
Antifungal Activity of Octyl Gallate: Structural Criteria and
Mode of Action
Isao Kubo,* Ping Xiao and Ken'ichi Fujita
Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720-3112, USA
Received 13 July 2000; accepted 16 November 2000
AbstractÐOctyl gallate (3,4,5-trihydroxybenzoate) was found to possess antifungal activity against Saccharomyces cerevisiae and
Zygosaccharomyces bailii, in addition to its potent antioxidant activity. Catechol moiety is essential to elicit this activity. The pri-
mary fungicidal activity of octyl gallate comes from its ability to act as a nonionic surface-active agent (surfactant). The length of
the alkyl chain is not a major contributor but plays an important role in eliciting the activity. # 2001 Elsevier Science Ltd. All
rights reserved.
In our continuing search for antimicrobial agents, pro-
pyl (C3) (1), octyl (C8) (2), and dodecyl (C12) (3) gallates
(see Fig. 1 for structures) were selected because these
three are currently permitted for use as antioxidant
additives in food and cosmetic products.1 Their anti-
microbial activity was ®rst tested against the 16 selected
microorganisms and the results are listed in Table 1. In
general, Gram-positive bacteria and fungi were suscep-
tible while Gram-negative bacteria were mostly resistant
to the gallates. Among the three gallates tested, octyl
gallate was found to exhibit fungicidal activity against
Saccharomyces cerevisiae, Zygosaccharomyces bailii,
Candida albicans, and Aspergillus niger, and was noticed
to be the only active compound against these fungi.
Hence, the current study was centered on modes of
fungicidal action of octyl gallate against S. cerevisiae as
an example. The activity against Z. bailii, a food spoil-
age yeast species, was also studied but to a lesser extent.
Octyl gallate was noted to be eective against S. cerevi-
siae with both minimum inhibitory concentration
(MIC) and minimum fungicidal concentration (MFC)
of 25 mg/mL (89 mM), suggesting no residual fungistatic
activity. The same gallate also exhibited antifungal
activity against Z. bailii with both MIC and MFC of 50
mg/mL (177 mM). In contrast, neither propyl nor dode-
cyl (lauryl) gallates showed any fungicidal activity
against the fungi tested. Notably, the fungicidal activity
of octyl gallate against S. cerevisiae and Z. bailii was not
in¯uenced by the pH values.
The head and tail structure and nonspeci®c anti-
microbial activity of octyl gallate are similar to those of
long chain alkanols in many aspects.2 However, addi-
tional functions may need to be considered for alkyl
gallates. For example, the ester group did not exist in
the alkanol structure and may be involved in eliciting
the additional activity. Since alkanols themselves exhibit
the antifungal activity against S. cerevisiae,3 the possi-
bility of S. cerevisiae exuding an esterase that hydro-
lyzes alkyl gallates to gallic acid and the corresponding
alkanols, was ®rst taken into account. This possibility
can be readily ruled out since none of the alkyl benzo-
ates, 4-hydroxybenzoates or 3,5-dihydroxybenzoates,
exhibited any antifungal activity against S. cerevisiae.
Analogues of octyl gallate were synthesized4 and tested
for their antifungal activity against S. cerevisiae for
comparison. Among them, octyl protocatechuate (3,4-
dihydroxybenzoate) (4) is the only compound to exhibit
the activity. As a result, both octyl 3,4,5-trihydroxy-
benzoate and octyl 3,4-dihydroxybenzoate showed the
activity and the potency is almost comparable. On the
other hand, octyl benzoate (5), octyl 2-hydroxybenzoate
(6), octyl 3-hydroxybenzoate (7), octyl 4-hydroxy-
benzoate (8), and octyl 3,5-dihydroxybenzoate (9)
exhibited no antifungal activity, indicating that catechol
or pyrogallol moieties are largely associated with the
activity. This can be supported by the fact that octyl 3-
hydroxy-4-methoxybenzoate (10) and octyl 4-hydroxy-
3-methoxybenzoate (11) no longer showed any anti-
fungal activity. On the basis of the data obtained, it
appears that a catechol moiety is prerequisite to elicit
*Corresponding author. Tel.: +1-510-643-6303; fax: +1-510-643-
0215; e-mail: ikubo@uclink4.berkeley.edu
0960-894X/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved.
PII: S0960-894X(00)00656-9