Multidrug resistance (MDR) is a great concern worldwide. There is a great need to develop new drugs with the potential to attack target cells that show MDR phenotype. The purpose of this study was to assess the reversing effect of new N-alkyl-3,4-diarylmaleimides on Bacillus subtilis resistant to rhodamine 6G as an indicator of its activity as modulators of efflux pumps and their additional potential as new antimicrobials. The efflux pump modulator effects of N-alkyl-3-4-diarylmaleimides were tested using the minimal inhibitory concentration (MIC) method on B. subtilis wild type and B. subtilis resistant to R6G, as well as on MDR bacteria isolated from clinical samples (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecium, and Acinetobacter baumannii). In addition, their antimicrobial activity was evaluated on clinical isolates. Five N-alkyl-3,4-diarylmaleimides showed the highest reversing activity on the resistance in the Bacillus model as well as with the bacteria isolated from clinical samples. Antimicrobial activity was observed in N-alkyl-3,4-diarylmaleimides against bacteria isolated from clinical samples. The results suggest that N-alkyl-3,4-diarylmaleimides have a potential activity in reversing MDR phenotype and as antimicrobials and may be considered as a potentially molecules to improve chemotherapy on resistant cells.

中文翻译：

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发现新的有效的基于N-烷基-3,4-二芳基马来酰亚胺的药物可逆转枯草芽孢杆菌对罗丹明6G的细菌抗性

多药耐药性（MDR）在世界范围内备受关注。迫切需要开发新的药物来攻击具有MDR表型的靶细胞。这项研究的目的是评估新的N-烷基-3,4-二芳基马来酰亚胺对若丹明6G耐药的枯草芽孢杆菌的逆转作用，以此作为其作为外排泵调节剂的活性及其作为新型抗菌剂的潜在潜力的指标。使用最小抑菌浓度（MIC）方法对枯草芽孢杆菌野生型和对R6G耐药的枯草芽孢杆菌以及从临床样品中分离出的MDR细菌使用N-烷基-3-4-二芳基马来酰亚胺的外排泵调节剂作用（大肠杆菌，金黄色葡萄球菌，铜绿假单胞菌，粪肠球菌和鲍曼不动杆菌）。此外，还对临床分离株评估了它们的抗菌活性。在芽孢杆菌模型以及从临床样品中分离出的细菌中，五种N-烷基-3,4-二芳基马来酰亚胺显示出对耐药性的最高逆转活性。在N-烷基-3,4-二芳基马来酰亚胺中观察到了对从临床样品中分离出的细菌的抗菌活性。结果表明，ñ-烷基-3,4-二芳基马来酰亚胺具有逆转MDR表型的潜在活性，并具有抗微生物作用，可以被视为改善耐药细胞化学疗法的潜在分子。