The role of small molecule-small molecule interactions in overcoming biological barriers for antibacterial drug action
The role of small molecule-small molecule interactions in overcoming biological barriers for antibacterial drug action
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DOI：
10.1007/s00214-006-0149-6
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发表时间：
2007-02-01
影响因子：
1.7
通讯作者：
Gibbons, Simon
中科院分区：
文献类型：
--
作者：
Zloh, Mire;Gibbons, Simon
抗生素对细菌的无效性可由多药耐药性（MDR）或由限制两亲化合物渗透到革兰氏阴性菌中的外膜引起。已经观察到在MDR调节剂存在下植物抗微生物剂对一系列MDR和革兰氏阴性细菌的显著活性（Tegos等人，Antimicrob Agents Chemother 46：3133，2002）。假设MDR的调节剂可能与外排泵的底物形成复合物，Biogr Med Chem Lett 14：881，2004），我们已经评估了Tegos等人（Antimicrob Agents Chemother 46：3133，2002）中报道的抗微生物剂和MDR调节剂之间的相互作用能。在本文中，我们可以证实，对外排泵诺拉在金黄色葡萄球菌的调节活性与MDR调节剂INF 271和抗菌药物之间的相互作用能相关。此外，配合物的log P的变化可能是负责克服革兰氏阴性菌的膜不透性，并在调节剂MC 207110的存在下增加抗菌活性。这表明小分子之间的相互作用可能在克服细菌中的生物屏障方面发挥重要作用。
The ineffectiveness of antibiotics against bacteria can be caused by multidrug resistance (MDR) or by an outer membrane, which restricts the penetration of amphipathic compounds into Gram-negative bacteria. Remarkable activities of plant antimicrobials in the presence of MDR modulators have been observed against a series of MDR and Gram-negative bacteria (Tegos et al., Antimicrob Agents Chemother 46:3133, 2002). Assuming that modulators of MDR might form complexes with substrates of efflux pumps Zloh et al., Biogr Med Chem Lett 14:881, 2004), we have evaluated interaction energies between antimicrobials and MDR modulators reported in Tegos et al. (Antimicrob Agents Chemother 46:3133, 2002). In this paper, we can confirm that modulation activity against the efflux pump NorA in Staphylococcus aureus correlates with the interaction energies between MDR modulator INF271 and antibacterials. Additionally, the change of log P of complexes might be responsible for overcoming the membrane impermeability in Gram-negative bacteria and increasing the antibacterial activity in the presence of the modulator MC207110. This suggests that interactions between small molecules may play an important role in overcoming biological barriers in bacteria.