Skip Navigation


JAC Advance Access originally published online on March 10, 2008
Journal of Antimicrobial Chemotherapy 2008 61(6):1270-1276; doi:10.1093/jac/dkn088
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
61/6/1270    most recent
dkn088v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kumar, A.
Right arrow Articles by Qazi, G. N.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kumar, A.
Right arrow Articles by Qazi, G. N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus

Ashwani Kumar1, Inshad Ali Khan1,*, Surrinder Koul2, Jawahir Lal Koul2, Subhash Chandra Taneja2, Intzar Ali1, Furqan Ali1, Sandeep Sharma1, Zahid Mehmood Mirza1, Manoj Kumar1, Pyare Lal Sangwan2, Pankaj Gupta2, Niranjan Thota2 and Ghulam Nabi Qazi1

1 Biotechnology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India 2 Bioorganic Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India

Received 6 November 2007; returned 7 January 2008; revised 10 February 2008; accepted 12 February 2008

* Corresponding author. Tel: +91-191-2569002; Fax: +91-191-2569333; E-mail: inshad{at}yahoo.com/iakhan{at}iiim.res.in

Objectives: Evaluation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus.

Methods: A library of piperine-derived compounds was evaluated for their potential to inhibit ethidium bromide efflux in NorA-overexpressing S. aureus SA 1199B. The active compounds were then individually combined with ciprofloxacin to study the potentiation of ciprofloxacin’s activity.

Results: Based on the efflux inhibition assay, a library of 200 compounds was screened. Three piperine analogues, namely SK-20, SK-56 and SK-29, were found to be the most potent inhibitors of the NorA efflux pump. These inhibitors acted in a synergistic manner with ciprofloxacin, by substantially increasing its activity against both NorA-overexpressing and wild-type S. aureus isolates. These analogues were 2- to 4-fold more potent than piperine at a significantly lower minimal effective concentration. Furthermore, these inhibitors also significantly suppressed the in vitro emergence of ciprofloxacin-resistant S. aureus.

Conclusions: A newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting.

Keywords: ciprofloxacin , microbial resistance , efflux pump inhibitors


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.