Topic: Applications of physics in new material technique development

Speaker: Professor Shouping Liu, Singapore Eye Research Institute

Time: 3:00 p.m., July 4, 2016

Venue: Conference Room 410, Building B12, SCUT South Campus

Abstract:

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.