Antibacterial peptidomimetic and characterization of its efficacy as an antibacterial and biocompatible coating for bioceramic-based bone substitutes

Abstract

Infection of orthopedic devices by pathogenic bacteria, coupled with the development of bacterial resistance against major antibiotics, have caused severe physical and emotional trauma to patients and posed economic challenges to healthcare institutes and governments worldwide. Antimicrobial peptidomimetics have emerged as promising new candidates to fight the rise of bacterial resistance. Conjugation of these peptidomimetics to bone implant materials has become a viable strategy to combat orthopedic device related infections. In this paper, we report on the synthesis of an anthranilamide-based antibacterial peptidomimetic. The compound, which could possibly be acting through the depolarization of bacterial cell membrane, demonstrated a higher toxicity towards S. aureus compared to E. coli. We further demonstrated the ability of this compound to disrupt pre-formed biofilms. Coating of the compound on hydroxyapatite discs was achieved via physical interactions between the charged hydroxyapatite surface and the peptidomimetic. This was confirmed via X-ray photoelectron spectroscopy. The compound imparted antibacterial property to the discs as determined via antibacterial assays and imaging, while rendering the discs mildly cytotoxic towards human fetal osteoblast cells.