Five novel cationic antimicrobial peptides (AMPs), inspired by natural motifs, were synthesized and evaluated against carbapenem-resistant clinical isolates of Escherichia coli. The AMPs varied in net charge (+4 to +8) and hydrophobicity. Minimal Inhibitory Concentration (MIC) assays revealed potent activity: AMP‑3 and AMP‑5 achieved MICs of 4 and 8 µg/mL, outperforming polymyxin B (MIC = 16 µg/mL).
Membrane permeabilization assays using propidium iodide showed rapid disruption within 30 minutes. Time‑kill curves indicated >99.9% bacterial reduction within 2 hours. Hemolysis tests and cytotoxicity on human keratinocytes confirmed selectivity: therapeutic indices were >10 for all peptides.
Stability tests revealed retained activity in up to 50% human serum and after exposure to proteases such as trypsin. These findings support further development of AMPs as alternatives to last‑resort antibiotics against multidrug‑resistant Gram‑negative pathogens.
