Antimicrobial Activity of Naturally Occurring Phenols and Derivatives Against Biofilm and Planktonic Bacteria

Abstract

Biofilm-forming bacteria present formidable challenges across diverse settings, and there is a need for new antimicrobial agents that are both environmentally acceptable and relatively potent against microorganisms in the biofilm state. The antimicrobial activity of three naturally occurring, low molecular weight, phenols, and their derivatives were evaluated against planktonic and biofilm Staphylococcus epidermidis and Pseudomonas aeruginosa. The structure activity relationships of eugenol, thymol, carvacrol, and their corresponding 2- and 4-allyl, 2-methallyl, and 2- and 4-n-propyl derivatives were evaluated. Allyl derivatives showed a consistent increased potency with both killing and inhibiting planktonic cells but they exhibited a decrease in potency against biofilms. This result underscores the importance of using biofilm assays to develop structure-activity relationships when the end target is biofilm.

Keywords: anti-biofilm; antimicrobial; biofilm; biofilm inhibition; essential oil.

Figure 1

Structures of parent compounds, thymol (1a), carvacrol (2a), and eugenol (3a) as well as allyl (1b/c, 2b/c, and 3b/e), 2-methallyl (1d, 2d, and 3g), and propyl (1e, 2e, and 3d/f) derivatives.

Scheme 1

Representative synthesis, using carvacrol (1a) and derivatives (1b−1d).

Figure 2

Time kill assays. Compounds were diluted in PBS and DMSO, (9.9:0.1), all controls were PBS and DMSO: (A) carvacrol, 2-allyl carvacrol, and a control with S. epidermidis, while the concentration of both carvacrol and 2-allyl carvacrol was 1.7 mM; (B) carvacrol, 2-allyl carvacrol, and a control with P. aeruginosa. While the concentration of both carvacrol and 2-allyl carvacrol was 15.6 mM; (C) thymol, 2-allyl thymol, and a control with S. epidermidis, at a concentration of 7.8 mM; (D) thymol, 2-allyl thymol, and a control with P. aeruginosa, at a concentration of 30 mM; (E) eugenol, “ortho eugenol,” guaiacol, and a control with S. epidermidis, at a concentration of 1.7 mM; (F) eugenol, “ortho eugenol,” guaiacol, and a control with P. aeruginosa, at a concentration of 15.6 mM.