Discovery of new effective N-alkyl-3,4-diarylmaleimides-based drugs for reversing the bacterial resistance to rhodamine 6G in Bacillus subtilis
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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.
KeywordsBacillus subtilis Multidrug resistance N-alkyl-3 4-Diarylmaleimides Antimicrobial
The authors thank the Directorate for Research Support and Postgraduate Programs (University of Guanajuato) for the financial support granted to Dra. Claudia Leticia Mendoza Macías and for the grant CIIC-054 -2018 of Convocatoria Institucional de Investigación Científica 2018. We gratefully acknowledge Aidee Guadalupe Aguilar Granados, Claudia Teresa Carranza López and Sarahí Montserrat García Miranda for their contribution in antimicrobial assays for this work.
Compliance with ethical standards
Conflict of interest
There are no conflicts of interest to declare.
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