title: 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.
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470, Eskisehir, Turkey.
authors.forename: Ulviye Acar
authors.initials: UA
authors.lastname: Cevik
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470, Eskisehir, Turkey.
authors.forename: Begum Nurpelin
authors.initials: BN
authors.lastname: Saglik
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, P.O. Box: 26470, Eskisehir, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ozkay
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Microbiology 26470, Eskisehir, Turkey.
authors.forename: Zerrin
authors.initials: Z
authors.lastname: Canturk
authors.affiliation: Bioprospecting Development and Consulting, Bogota, Colombia.
authors.forename: Juan
authors.initials: J
authors.lastname: Bueno
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmacognosy, 26470, Eskisehir, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Demirci
authors.affiliation: Anadolu University, Faculty of Engineering, Department of Environmental Engineering, Eskisehir, Turkey.
authors.forename: Ali Savas
authors.initials: AS
authors.lastname: Koparal
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D008872:Microwaves; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D001562:Benzimidazoles
keywords: Benzimidazole; Escherichia coli; antimicrobial; hydrazone; mass spectroscopy; nifuroxazide