Kumar Ashwani, Khan Inshad Ali, Koul Surrinder, Koul Jawahir Lal, Taneja Subhash Chandra, Ali Intzar, Ali Furqan, Sharma Sandeep, Mirza Zahid Mehmood, Kumar Manoj, Sangwan Pyare Lal, Gupta Pankaj, Thota Niranjan, Qazi Ghulam Nabi
Biotechnology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
J Antimicrob Chemother. 2008 Jun;61(6):1270-6. doi: 10.1093/jac/dkn088. Epub 2008 Mar 10.
Evaluation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus.
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.
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.
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.
评估胡椒碱的新型合成类似物作为金黄色葡萄球菌多药外排泵NorA抑制剂的效果。
评估一组胡椒碱衍生化合物抑制过表达NorA的金黄色葡萄球菌SA 1199B中溴化乙锭外排的潜力。然后将活性化合物分别与环丙沙星联合，研究环丙沙星活性的增强情况。
基于外排抑制试验，筛选了一个包含200种化合物的文库。发现三种胡椒碱类似物，即SK - 20、SK - 56和SK - 29，是NorA外排泵最有效的抑制剂。这些抑制剂与环丙沙星协同作用，通过大幅提高其对过表达NorA和野生型金黄色葡萄球菌分离株的活性。这些类似物在显著更低的最小有效浓度下比胡椒碱效力高2至4倍。此外，这些抑制剂还显著抑制了环丙沙星耐药金黄色葡萄球菌的体外出现。
一类新鉴定的源自天然酰胺胡椒碱的化合物，在通过抑制NorA外排泵增强环丙沙星活性方面比母体分子更有效。这些分子可能在临床环境中增强氟喹诺酮类药物的抗菌活性方面证明有用。
