icaritin and Keratitis

A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has been designed from natural icaritin to combat drug-resistant Gram-positive bacterial infections. Compound 6 containing two arginine residues exhibited excellent antibacterial activity against Gram-positive bacteria, including MRSA, and very low toxicity to mammalian cells, resulting in a high selectivity of more than 511, comparable to that of several membrane-active antibiotics in clinical trials. Our data show for the first time that icaritin derivatives effectively kill bacteria. Meanwhile, this is the first study deploying a biomimicking strategy to design potent flavone-based membrane targeting antimicrobials. 6 showed rapid bactericidal activity by disrupting the bacterial membrane and can circumvent the development of bacterial resistance. Importantly, 6 was highly efficacious in a mouse model of corneal infection caused by MRSA and Staphylococcus aureus.

Topics: Animals; Anti-Bacterial Agents; Arginine; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Membrane; Cell Survival; Drug Resistance, Bacterial; Fibroblasts; Flavones; Hemolysis; Humans; Keratitis; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred C57BL; Microbial Sensitivity Tests; Molecular Mimicry; Rabbits; Staphylococcus aureus; Structure-Activity Relationship