Effect of plant-based catecholic molecules on the prevention and eradication of Escherichia coli biofilms: A structure activity relationship study

Abstract

Persistent bacterial infections and increased resistance to multidrugs are mostly related with biofilm formation which constitute a global concern in nowadays society. Therefore, studies must be conducted in order to discover more efficient antibiofilm agents. Nine compounds with a catecholic moiety (catechol (CAT), veratrol (VER), guaiacol (GUA), 2-ethoxphenol (ETH), 4-methylcatechol (MEC), 4-tert-butylcatechol (TEB), pyrogallol (PYR), 3-methoxycatechol (MET), and o-phenylene-phosphochloridite (OPP)) were investigated for their potential to prevent and eradicate Escherichia coli biofilms. Their action was assessed on biomass and metabolic activity, sessile cells' membrane integrity and culturability, motility and cell surface hydrophobicity (CSH). ETH, MEC, TEB, PYR and OPP exhibited the best antibiofilm activities among the tested catechols, inducing biofilm removal and metabolic inactivation, sessile cells' membrane disruption and death. CAT, TEB and PYR significantly inhibited E. coli swimming motility. Likewise, ETH, MEC, TEB and PYR significantly reduced E. coli CSH. An additive interaction of combined catechols with ciprofloxacin was attained in both control and preventive strategies. From a structure activity relationship (SAR) study, an increase in the hydrocarbon side chain and lipophilicity using ETH and TEB as scaffolds is suggested for increased activity. Hydroxyl groups are also suggested to be particularly related to their antibiofilm activity. All the catechols fulfil the Lipinski's “rule of five” requisites and thus are promising scaffolds in the development of new formulations for therapeutic purposes.