Novel antibacterial, antioxidant, and anti-inflammatory aminated chitosan hybrid quinoline Schiff base as multi-target agent: Design, molecular docking, and toxicity assessment

Abstract

This study involves the synthesis of a novel 7-ethoxy-3-formyl-2-morpholino quinoline (MQ) derivative, which was hybridized with aminated chitosan (AMCH) to yield a new AMCH-MQ Schiff base. Structural characterization via ¹H NMR, FTIR, electronic spectra, XRD, and TGA confirmed successful hybridization. Ion exchange capacity decreased from 28.88 m_eq/g (AMCH) to 15.71 m_eq/g (AMCH-MQ), verifying covalent modification. Antibacterial efficacy against E. coli (Gram-negative) and S. haemolyticus (Gram-positive) exhibited dose-dependent enhancement, with inhibition zones reaching 43 mm and 35 mm, respectively, and a minimal inhibitory concentration (MIC) of 0.625 mg/mL. At 10 mg/mL, AMCH-MQ (2) suppressed 95 % of bacterial growth. The derivative demonstrates notable antioxidant activity, effectively scavenging free radicals at 46 %, surpassing AMCH's 26 % capacity. A dose-dependent increase in hemolysis inhibition was accomplished, reaching 84.8 %, indicating adequate anti-inflammatory activity. Toxicity predictions indicated a minimal risk of systemic adverse effects, supporting the in vitro cytotoxicity assays that validated the safety profile of AMCH-MQ, which showed a positive correlation with quinoline content. Molecular docking simulations identified robust interactions between AMCH-MQ and key enzymatic targets (DHFR, QSR, DNA gyrase), supported by favorable binding affinities and interaction diversity. These findings position AMCH-MQ as a non-toxic multi-bioactive agent with synergistic antibacterial, antioxidant, and anti-inflammatory properties.