NOVEL MEMBRANE TARGETING ANTIMICROBIALS FOR DRUG-RESISTANT PATHOGENS

Abstract

ANTIBIOTIC RESISTANCE IS A CRITICAL GLOBAL HEALTH CARE CRISIS, WHICH REQUIRES URGENT ACTION TO DEVELOP MORE EFFECTIVE ANTIBIOTICS. THIS STUDY HAS DESIGNED AND TESTED TWO NOVEL MEMBRANE TARGETING ANTIMICROBIALS, WHICH ARE EFFECTIVE AGAINST DRUG-RESISTANT (DR) AND MULTIDRUG-RESISTANT (MDR) RESISTANT PATHOGENS: AMPHIPHILIC XANTHONE DERIVATIVES AND N-LIPIDATED PEPTIDE DIMERS. UTILIZING THE HYDROPHOBIC SCAFFOLD OF XANTHONE, A NUMBER OF POTENT AMPHIPHILIC XANTHONE DERIVATIVES AGAINST GRAM-POSITIVE BACTERIA WERE DEVELOPED. IN GENERAL, SPECIFIC MOLECULAR COMPONENTS ATTACHED TO A CORE MOLECULE WERE REQUIRED TO MIMIC THE MEMBRANE-TARGETING ACTION OF AN ANTIMICROBIAL CATIONIC PEPTIDE. IN ADDITION, IN THIS STUDY, A SERIES OF N-LIPIDATED PEPTIDE-DIMERS (CN-B2088) THAT DISPLAYED POTENT ANTIMICROBIAL ACTIVITIES AGAINST GRAM-NEGATIVE BACTERIA, INCLUDING CARBAPENEM-RESISTANT ENTEROBACTERIACEAE (CRE) WERE IDENTIFIED. THESE COMPOUNDS DISPLAYED POTENT ANTIMICROBIALS WITH DESIRABLE PROPERTIES WHICH INCLUDE