Synthesis of New Fluoro-Benzimidazole Derivatives as an Approach towards the Discovery of Novel Intestinal Antiseptic Drug Candidates

Abstract

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.

Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

“…[16] This discovery has had a substantial impact on medical chemistry. These compounds' acetylcholinesterases, [17] anticancer, [18] α-glucosidase, [19] antitubercular, [20] anti-mitotic, [21] antimicrobial, [22] and antifungal [23] properties are also of great interest.…”

Human intestinal models to study interactions between intestine and microbes

“…Two non-tumour intestinal cell lines with epithelial phenotypes (FHC CRL-1831 and CCD 841 CoN) have been, respectively, used to evaluate the effective antimicrobial activity of nanocomposites against Escherichia coli and Staphylococcus aureus [58], or to demonstrate the positive effect of several probiotics to decrease the adhesion of several Clostridium difficile strains [59]. Likewise, the low cytotoxicity effect of 19 new fluoro-benzimidazole derivatives was demonstrated in cell line CCD 841 CoN, in contrast to the high inhibitory activity of those molecules against Escherichia coli O157:H7, Escherichia coli ATCC 8739 Escherichia coli ATCC 35218 and Salmonella typhimurium ATCC 1331 [60]. The culture of tumour cells is a much more popular system to study cellular physiology during infection.…”

Synthesis and Molecular Drug Validations of 1H-Benzo[d]imidazol-2-amine Derivatives: Molecular Docking and its Biological Activities

“…Among a range of different chemical entities, benzoimidazoles/benzimidazoles are notable with higher medicinal values [3]. Benzimidazoles have showed a range of biological activities starting from antituberculosis [4], anticancer [5], antimicrobial [6], intestinal antiseptic [7], antidiabetic [8], etc. Their flexibility in electron exchange between various electron donor and acceptors between the receptors making benzimidazoles as a chief inhibitors based therapeutic agents.…”