Meldrum's acid derivates are MepA efflux pump inhibitors: In vitro and in silico essays

被引:0
作者
Araujo, Isaac Moura [1 ]
Pereira, Raimundo Luiz Silva [1 ]
de Araujo, Ana Carolina Justino [1 ]
Goncalves, Sheila Alves [2 ]
Tintino, Saulo Relison [1 ]
Oliveira-Tintino, Cicera Datiane de Morais [1 ]
de Menezes, Irwin Rose Alencar [1 ]
Salamoni, Renata [3 ]
Begnini, Ieda Maria [3 ]
Rebelo, Ricardo Andrade [3 ]
Silva, Luiz Everson da [4 ]
Gurgel, Ana Pavla Almeida Diniz [5 ]
Coutinho, Henrique Douglas M. [1 ,6 ]
机构
[1] Reg Univ Cariri URCA, Dept Chem Biol, Crato, Ceara, Brazil
[2] Reg Univ Cariri URCA, Dept Biol, Crato, Ceara, Brazil
[3] Reg Univ Blumenau FURB, Dept Chem, Blumenau, SC, Brazil
[4] Fed Univ Parana UFPR, Res, Matinhos, Parana, Brazil
[5] Univ Fed Paraiba, Dept Engn & Environm, Joao Pessoa, Paraiba, Brazil
[6] Reg Univ Cariri URCA, Lab Microbiol & Mol Biol, BR-63105000 Crato, CE, Brazil
关键词
antibacterial; eflux pump; Meldrum acid derivates; MepA; STAPHYLOCOCCUS-AUREUS; MULTIDRUG-RESISTANCE; ETHIDIUM-BROMIDE; MELDRUMS ACID; IDENTIFICATION; EXPRESSION; BACTERIA;
D O I
10.1002/jobm.202300558
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Efflux pumps are proteins capable of expelling antibiotics from bacterial cells, have emerged as a major mechanism of bacterial resistance. In the ongoing pursuit to overcome and reduce bacterial resistance, novel substances are being explored as potential efflux pump inhibitors. Meldrum's acid, a synthetic molecule widely studied for its role in synthesizing bioactive compounds, holds promise in this regard. Therefore, the objective of this study is to evaluate the antibacterial activity of three derivatives of Meldrum's acid and assess their ability to inhibit efflux mechanisms, employing both in silico and in vitro approaches. The antibacterial activity of the derivatives was assessed using a broth microdilution testing method. Surprisingly, the derivatives did not exhibit direct antibacterial activity on their own. However, they displayed a significant effect in enhancing the efficacy of antibiotics, suggesting a potential role in potentiating their effects. Furthermore, fluorescence emission assays using ethidium bromide indicated that the derivatives could potentially block efflux pumps, as they exhibited fluorescence levels comparable to the positive control. To further investigate their inhibitory capacity, molecular docking studies were conducted in silico, revealing binding interactions similar to ciprofloxacin and carbonyl cyanide 3-chlorophenylhydrazone, known efflux pump inhibitors. These findings highlight the potential of Meldrum's acid derivatives as effective inhibitors of efflux pumps. By targeting these mechanisms, the derivatives offer a promising avenue to enhance the effectiveness of antibiotics and combat bacterial resistance. This study underscores the importance of exploring novel strategies in the fight against bacterial resistance and provides valuable insights into the potential of Meldrum's acid derivatives as efflux pump inhibitors. Further research and exploration in this field are warranted to fully exploit their therapeutic potential.
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页数:12
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