Feleucin-K3 Analogue with an α-(4-Pentenyl)-Ala Substitution at the Key Site Has More Potent Antimicrobial and Antibiofilm Activities in Vitro and in Vivo

• DOI: 10.1021/acsinfecdis.0c00545
• Publication Date: 2020-12-10T00:31:08Z
• Authors: Xiaomin Guo; Jing Rao; Tiantian Yan; Bangzhi Zhang; Wenle Yang; Wangsheng Sun; Junqiu Xie
• Keywords: Mechanism of Action

The development of antimicrobial compounds is now regarded as an urgent problem. Antimicrobial peptides (AMPs) have great potential to become novel drugs. Feleucin-K3 α-helical cationic AMP isolated from the skin secretion Asian bombinid toad species Bombina orientalis and has activity. In our previous studies, amino acid scanning was performed determine key site affecting its this study, we investigated synthesized a series analogues that either natural or unnatural hydrophobic substitution at fourth residue Feleucin-K3. Among these analogues, Feleucin-K59 (K59), which α-(4-pentenyl)-Ala substitution, shown increased activity against both standard drug-resistant strains clinical common bacteria, improved stability, no hemolytic concentrations, resistance. addition, K59 potent antibiofilm in vitro. More importantly, showed better activities bacteria vivo experiments mice than traditional antibiotics. preliminary study mechanism action, found could rapidly kill by dual-action disrupting cell membrane binding intracellular DNA, thus making it difficult for develop