Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Nov 5;51(45):11254-7.
doi: 10.1002/anie.201206911. Epub 2012 Oct 9.

Potent small-molecule suppression of oxacillin resistance in methicillin-resistant Staphylococcus aureus

Tyler L Harris  1 , Roberta J Worthington, Christian Melander
Affiliations

Potent small-molecule suppression of oxacillin resistance in methicillin-resistant Staphylococcus aureus

Tyler L Harris et al. Angew Chem Int Ed Engl. .

Abstract

Shields down! Adjuvant molecules that have the ability to restore the susceptibility of multi-drug-resistant bacteria, such as MRSA, to clinically available antibiotics are a promising alternative to the development of novel antimicrobials. Pictured is a potent small molecule (1) that, at sub-minimum inhibitory concentration (sub-MIC) levels, lowers the MIC of oxacillin (2) against a number of MRSA strains by up to 512-fold.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Time-kill curves for USA300 MRSA strain JE2. Solid lines: no 2-AIT, broken lines: 5 µM 7d. Black: no oxacillin, blue: 64 µg/mL oxacillin, red: 16 µg/mL oxacillin, green: 4 µg/mL oxacillin, purple: 1 µg/mL oxacillin.
Scheme 1
Scheme 1
Synthesis of N1-substituted 2-AITs. Reagents and conditions: a) tBuOK, THF, −78 °C–rt 72 h; b) N-(2-azidoethyl)-4-pentylbenzamide, CuSO4, sodium ascorbate, H2O/EtOH/CH2Cl2, rt 3 h; c) 2 M HCl/Et2O, rt, 2 h; d)i RCHO, LiOH.H2O, MeOH, rt 2 h, ii NaBH4, rt, 1 h; e) Boc2O, TMAH, CH3CN, rt, 16 h; f) HN(OMe)Me.HCl, iPrMgCl, THF, −20 °C–rt, 18 h; g) DIBAL-H, THF, −78 °C, 2 h; h) 9:1 CH2Cl2/TFA, rt, 15 min; i) H2O/EtOH, pH 4.3, H2NCN, 95 °C, 3 h.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Eiland EH, Gatlin DJ., III Pharmacy Practice. 2008;21:313–318.
    1. *IDSA Policy Paper d CID. 2011;52(Suppl 5):d S397. - PubMed
    1. O’Hara FP, Amrine-Madsen H, Mera RM, Brown ML, Close NM, Suaya JA, Acosta CJ. Microb. Drug Resistance. 2012 - PubMed
    1. Coates ARM, Halls G, Hu Y. Brit. J. Pharmacol. 2011;163:184–194. - PMC - PubMed
    1. Dolgin E. Nat. Med. 2010;16:1054–1054. - PubMed

Publication types

MeSH terms