ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Discovery of new effective N-alkyl-3,4-diarylmaleimides-based drugs for reversing the bacterial resistance to rhodamine 6G in Bacillus subtilis

Claudia Leticia Mendoza-Macías, Cesar Rogelio Solorio-Alvarado, Angel Josabad Alonso-Castro, Clara Alba-Betancourt, Martha Alicia Deveze-Álvarez, Felipe Padilla-Vaca, and Arturo Reyes-Gualito

División de Ciencias Naturales y Exactas, Departamento de Farmacia, Universidad de Guanajuato, Guanajuato, Mexico

E-mail: cl.mendoza@ugto.mx

Received: 3 May 2019  Accepted: 8 November 2019

Abstract:

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.

Keywords: Bacillus subtilis; Multidrug resistance; N-alkyl-3; 4-Diarylmaleimides; Antimicrobial

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-019-00992-7

Chemical Papers 74 (5) 1429–1438 (2020)