An innovative strategy to treat pathogenic biofilm-associated infections in vitro and in vivo using guanidinium-linked neomycin lipidation

Published in: RSC Med. Chem., 2025,16, 6109-6123

DOI: 10.1039/D5MD00776C

Authors: Sourav Sarkar, Vedant Tripathi, Surajit Sadhukhan [TCGLS Member], Jhuma Bhadra and Santanu Bhattacharya

Abstract: To overcome neomycin’s limited efficacy against complex Gram-positive and Gram-negative co-infections, we have developed a novel guanidinium-linked neomycin–lipid conjugate (guanidino Neo-lipid). This multifunctional construct integrates three synergistic components: a neomycin core for ribosomal targeting, a hydrophobic lipid chain to facilitate membrane interaction and cellular uptake, and a cationic guanidinium moiety that enhances electrostatic binding to negatively charged bacterial membranes. The resulting conjugate demonstrates significantly improved antibacterial activity in liquid cultures and effectively disrupts biofilm formation. This approach offers a promising therapeutic strategy for treating persistent infections caused by both Gram-positive and Gram-negative pathogens, including co-infective scenarios.