Format

Send to

Choose Destination
Br J Pharmacol. 2006 Nov;149(5):551-9. Epub 2006 Sep 18.

Small molecules with antimicrobial activity against E. coli and P. aeruginosa identified by high-throughput screening.

Author information

1
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0521, USA.

Abstract

BACKGROUND AND PURPOSE:

New antimicrobials are needed because of the emergence of organisms that are resistant to available antimicrobials. The purpose of this study was to evaluate a high-throughput screening approach to identify antibacterials against two common disease-causing bacteria, and to determine the frequency, novelty, and potency of compounds with antibacterial activity.

EXPERIMENTAL APPROACH:

A high-throughput, turbidometric assay of bacterial growth in a 96-well plate format was used to screen a diverse collection of 150,000 small molecules for antibacterial activity against E. coli and P. aeruginosa. The statistical Z'-factor for the assay was > or = 0.7.

KEY RESULTS:

Screening for inhibition of E. coli growth gave a 'hit' rate (> 60% inhibition at 12.5 microM) of 0.025%, which was more than 5-fold reduced for P. aeruginosa. The most potent antibacterials (EC50 < 0.5 microM) were of the nitrofuran class followed by naphthalimide, salicylanilide, bipyridinium and quinoazolinediamine chemical classes. Screening of > 250 analogs of the most potent antibacterial classes established structure-activity data sets.

CONCLUSIONS AND IMPLICATIONS:

Our results validate and demonstrate the utility of a growth-based phenotype screen for rapid identification of small-molecule antibacterials. The favourable efficacy and structure-activity data for several of the antibacterial classes suggests their potential development for clinical use.

PMID:
16981005
PMCID:
PMC2014677
DOI:
10.1038/sj.bjp.0706873
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center