N-Glycidyl d-tryptophan ether-based ointment with anti-infective, anti-inflammatory, and wound-healing properties†

Abstract

Anti-infective hydrogel is an emerging and innovative material used as an antibacterial ointment or to coat medical devices. Here, we synthesized a novel derivative of N-glycidyl D-tryptophan ether using the D-isoform of tryptophan through a ring-opening polymerization reaction. The compound was characterized using gel permeation chromatography (GPC), HPLC, ¹H NMR, ¹³C NMR, MALDI-TOF-MS, and FTIR spectroscopy. The results demonstrated its antibacterial activity by inhibiting quorum sensing and subsequent biofilm formation. In vivo studies revealed the ability of the compound to promote wound healing by reducing inflammatory cytokine levels, such as tumor necrosis factor alpha, interleukin-1β, and IL-6. Moreover, the compound showed antioxidant activity by scavenging the DPPH radical due to the presence of polymeric hydroxyl acidic protons near the nitrogen. Since inflammation prompted ROS-initiated DNA strand breaks, it was also confirmed that the compound could reduce DNA strand break accumulation, as demonstrated through testing against bleomycin-induced DNA strand break accumulation. Therefore, the synthesized compound, which could be used as a base material for ointments, was found to be effective for antibacterial and wound healing actions by (a) inhibiting biofilm formation by bacteria, (b) reducing the expression of inflammatory cytokines, and (c) preventing the accumulation of DNA strand breaks through free-radical scavenging activity.