新加坡眼科研究所刘寿平研究员：Synthetic Xanthone Amphiphiles as Antibiotics with Therapeutic Potential

 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。