当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Amino acid modified xanthone derivatives: novel, highly promising membrane-active antimicrobials for multidrug-resistant Gram-positive bacterial infections.

Amino acid modified xanthone derivatives: novel, highly promising membrane-active antimicrobials for multidrug-resistant Gram-positive bacterial infections.

Abstract：

:Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compounds 5c and 6, which contain a hydrophobic xanthone core, lipophilic chains, and cationic amino acids, 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. 5c and 6 were effective in a mouse model of corneal infection by S. aureus and MRSA. Evidence is presented indicating that 5c and 6 target the negatively charged bacterial membrane via a combination of electrostatic and hydrophobic interactions. These results suggest that 5c and 6 have significant promise for combating life-threatening infections.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Koh JJ,Lin S,Aung TT,Lim F,Zou H,Bai Y,Li J,Lin H,Pang LM,Koh WL,Salleh SM,Lakshminarayanan R,Zhou L,Qiu S,Pervushin K,Verma C,Tan DT,Cao D,Liu S,Beuerman RW

doi

10.1021/jm501285x

subject

Has Abstract

pub_date

2015-01-22 00:00:00

pages

739-52

issue

2

eissn

0022-2623

issn

1520-4804

journal_volume

58

pub_type

杂志文章

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