Juan Bueno

Infectious diseases caused by bacteria, viruses, parasites and fungi, and their interaction with hosts and the environment are a global public health threat. In antimicrobial drug discovery from natural products, this potentiation of the antibiotic activity has been described as in the case of clavulanic acid and recently ellagic and tannic acids against multidrug-resistant microorganisms (MDR) strains of Acinetobacter baumannii. Biofilms are microbial communities attached on a surface, which are embedded in a matrix that provides a reservoir for microbial cells and confers a protection against biocides and drugs contributing to drug resistance development. Several foodborne diseases are caused by bacterial toxins that negatively affect the quality of foods, therefore the search for inhibitors is required to ensure the safety of the foods. Synergy research of the mixture of bioactive constituents can improve the application of phytopharmaceuticals in antimicrobial drug discovery programs. EOs are sensitive materials which can easily suffer degradation under the action of oxygen, light and moderate temperatures.

In the present study, nineteen new fluoro-benzimidazole derivatives, including nifuroxazide analogs, were synthesized by microwave-supported reactions and tested against a panel of pathogenic microorganisms consisting of resistant strains. The synthesized compounds were characterized and identified by FT-IR, 1H- and 13C-NMR, mass spectroscopy, and elemental analyses, respectively. In vitro antimicrobial and cytotoxic effects of the synthesized compounds were determined by microdilution and by [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] (MTT) assay. The compound 4-[5(6)-fluoro-1H-benzimidazol-2-yl)-N'-(2- methylbenzylidene)]benzohydrazide (18) showed particularly high inhibitory activity against the gastro-intestinal pathogens, such as Escherichia coli O157:H7, Escherichiacoli ATCC 8739, Escherichia coli ATCC 35218 and Salmonella typhimurium ATCC 13311 standard strains, with minimum inhibitory concentrations (MIC90) ranging from 0.49–0.98 μg/mL. The microbial panel contained a total of ten pathogens including Klebsiella sp., Mycobacterium sp., MRSA, etc., for which the level of inhibitory activity measured was higher than that exhibited by the tested concentrations (MIC > 1000 μg/mL). In vitro cytotoxicity results revealed that the inhibitory concentration (IC50) value (210.23 μg/mL) of compound 18 against CCD 841 CoN cells (human intestinal epithelial cell line) is about 430 times higher than its MIC90 value against the tested Escherichia coli strains. Furthermore, the docking study of compound 18 suggested that its structure is very compatible with the active site pocket of the phosphofructokinase-2 enzyme.