新加坡眼科研究所刘寿平研究员:Synthetic Xanthone Amphiphiles as Antibiotics with Therapeutic Potential
日期:2018-03-27 浏览量:25

时间:2016年7月4日(星期一)下午15:00
地点:大学城校区B12-410会议室

报告摘要:
       Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. This talk first describes how to tune the amphiphilic conformation of α-mangostin, a natural compound with a hydrophobic nature of xanthone to improve the antimicrobial activity and selectivity for Gram-positive bacteria. A series of xanthone derivatives were obtained by cationic modification of free hydroxyl groups of α-mangostin at C3 and C6 positions with amines groups of different pKa values. This strategy provides a new insight to improve “hits” in the development of new membrane-active antibiotics for drug-resistant pathogens.
       Further utilizing the hydrophobic scaffold of natural or synthetic xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antibiotics. Compounds AM-052 and AM-218, which contain a hydrophobic xanthone core, lipophilic chains and cationic arginine residues, displayed very promising antimicrobial activity against multidrug-resistant Gram-positive bacteria, including MRSA and VRE, rapid time-kill, avoidance of antibiotic resistance and low toxicity. The bacterial membrane selectivity of these molecules was comparable to that of several membrane-targeting antibiotics in clinical trials. The two lead compounds and other xanthone compounds were effective in a mouse model of corneal infection by S. aureus, MRSA, Pseudomonas aeruginosa and even mycobacteria. These results suggest that the lead compounds have significant promise for combating life-threatening infections. This seminar also summarizes development of small molecules based membrane-targeting antibiotics in the clinical trials.

附报告人简介:
       刘寿平研究员的研究领域包括研究和开发以病原体细胞膜为靶点的新一代膜活性抗生素,克服超级病菌,包括细菌,真菌和结核菌的多重抗药性; 具有抗菌活性的医用植入材料; 含胍基, 胺基,多胺基化合物 和多酚类化合物的抗生物膜活性; 功能性荧光高分子/聚合物的设计,合成和应用等。目前他在J. Med. Chem.,Sci. Rep., Antimicrob. Agents, Chemother., J. Biol. Chem., Biochemistry, Macromolecules等期刊上发表学术论文40余篇,申请发明专利6项。


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