Non-leaching antimicrobial surfaces through polydopamine bio-inspired coating of quaternary ammonium salts or an ultrashort antimicrobial lipopeptide.

Bacterial fouling on surfaces significantly increases the resistance of bacteria toward antibiotics, which leads to medical complications and a corresponding financial burden. Here, we report on a general and robust technique for facile modification of various surfaces with different antibacterial agents. Our approach in this study was inspired by the strong adhesion of mussel adhesion proteins (MAPs) to many types of surfaces, including metals, polymers, and inorganic materials. Thus, glass and polymeric slides were dip-coated with dopamine, as a MAP mimic, and the resulting surfaces were characterized. The reactivity of dopamine-coated surfaces toward nucleophilic addition was then confirmed by reacting them with fluorescent probes containing either a free amino or a free thiol group. Laser scanning confocal microscopy (LSCM), X-ray photoelectron spectroscopy (XPS), confocal Raman microscopy, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectroscopy, and cyclic voltammetry studies collectively suggested that the probes had covalently attached to the surfaces. Fabrication of dopamine-coated surfaces with an antibacterial quaternary amine or an ultrashort lipopeptide analog generated surfaces that effectively kill Escherichia coli and Staphylococcus aureuscells on contact. Moreover, minimal leaching of the fabricated agent was detected after prolonged incubation. This technique could be further developed to a "paint-like" or self-assembling monolayer-like procedure for the preparation of antibacterial surfaces on various materials

Non-leaching antimicrobial surfaces through polydopamine bio-inspired coating of quaternary ammonium salts or an ultrashort antimicrobial lipopeptide.

Bacterial fouling on surfaces significantly increases the resistance of bacteria toward antibiotics, which leads to medical complications and a corresponding financial burden. Here, we report on a general and robust technique for facile modification of various surfaces with different antibacterial agents. Our approach in this study was inspired by the strong adhesion of mussel adhesion proteins (MAPs) to many types of surfaces, including metals, polymers, and inorganic materials. Thus, glass and polymeric slides were dip-coated with dopamine, as a MAP mimic, and the resulting surfaces were characterized. The reactivity of dopamine-coated surfaces toward nucleophilic addition was then confirmed by reacting them with fluorescent probes containing either a free amino or a free thiol group. Laser scanning confocal microscopy (LSCM), X-ray photoelectron spectroscopy (XPS), confocal Raman microscopy, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectroscopy, and cyclic voltammetry studies collectively suggested that the probes had covalently attached to the surfaces. Fabrication of dopamine-coated surfaces with an antibacterial quaternary amine or an ultrashort lipopeptide analog generated surfaces that effectively kill Escherichia coli and Staphylococcus aureuscells on contact. Moreover, minimal leaching of the fabricated agent was detected after prolonged incubation. This technique could be further developed to a "paint-like" or self-assembling monolayer-like procedure for the preparation of antibacterial surfaces on various materials

A Tale of Switched Functions: From Cyclooxygenase Inhibition to M-Channel Modulation in New Diphenylamine Derivatives

Cyclooxygenase (COX) enzymes are molecular targets of nonsteroidal anti-inflammatory drugs (NSAIDs), the most used medication worldwide. However, the COX enzymes are not the sole molecular targets of NSAIDs. Recently, we showed that two NSAIDs, diclofenac and meclofenamate, also act as openers of Kv7.2/3 K+ channels underlying the neuronal M-current. Here we designed new derivatives of diphenylamine carboxylate to dissociate the M-channel opener property from COX inhibition. The carboxylate moiety was derivatized into amides or esters and linked to various alkyl and ether chains. Powerful M-channel openers were generated, provided that the diphenylamine moiety and a terminal hydroxyl group are preserved. In transfected CHO cells, they activated recombinant Kv7.2/3 K+ channels, causing a hyperpolarizing shift of current activation as measured by whole-cell patch-clamp recording. In sensory dorsal root ganglion and hippocampal neurons, the openers hyperpolarized the membrane potential and robustly depressed evoked spike discharges. They also decreased hippocampal glutamate and GABA release by reducing the frequency of spontaneous excitatory and inhibitory post-synaptic currents. In vivo, the openers exhibited anti-convulsant activity, as measured in mice by the maximal electroshock seizure model. Conversion of the carboxylate function into amide abolished COX inhibition but preserved M-channel modulation. Remarkably, the very same template let us generating potent M-channel blockers. Our results reveal a new and crucial determinant of NSAID-mediated COX inhibition. They also provide a structural framework for designing novel M-channel modulators, including openers and blockers