Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus
IR@IIIM: CSIR-Indian Institute of Integrative Medicine, Jammu
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| Title |
Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus
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| Creator |
Kumar, A.
Khan, I. A. Koul, S. Koul, J. L. Taneja, S. C. Ali, I. Ali, F. Sharma, S. Mirza, Z. M. Kumar, M. Sangwan, P. L. Gupta, P. Thota, N. Qazi, G. N. |
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| Subject |
Pharmacological Sciences
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| Description |
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.
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| Date |
2008
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://iiim.csircentral.net/302/1/10.1093jacdkn088.pdf
Kumar, A. and Khan, I. A. and Koul, S. and Koul, J. L. and Taneja, S. C. and Ali, I. and Ali, F. and Sharma, S. and Mirza, Z. M. and Kumar, M. and Sangwan, P. L. and Gupta, P. and Thota, N. and Qazi, G. N. (2008) Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 61 (6). pp. 1270-1276. ISSN 0305-7453 |
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| Relation |
http://dx.doi.org/10.1093/jac/dkn088
http://iiim.csircentral.net/302/ |
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