Abstract
A desirable attribute of novel antimicrobial agents for bacterial diarrhea is decreased toxicity toward host intestinal microbiota. In addition, gut dysbiosis is associated with an increased risk of developing intestinal cancer. In this study, the selective growth-inhibitory activities of ten phytochemicals and their synthetic analogs (berberine, bismuth subsalicylate, ferron, 8-hydroxyquinoline, chloroxine, nitroxoline, salicylic acid, sanguinarine, tannic acid, and zinc pyrithione), as well as those of six commercial antibiotics (ceftriaxone, ciprofloxacin, chloramphenicol, metronidazole, tetracycline, and vancomycin) against 21 intestinal pathogenic/probiotic (e.g., Salmonella spp. and bifidobacteria) bacterial strains and three intestinal cancer/normal (Caco-2, HT29, and FHs 74 Int) cell lines were examined in vitro using the broth microdilution method and thiazolyl blue tetrazolium bromide assay. Chloroxine, ciprofloxacin, nitroxoline, tetracycline, and zinc pyrithione exhibited the most potent selective growth-inhibitory activity against pathogens, whereas 8-hydroxyquinoline, chloroxine, nitroxoline, sanguinarine, and zinc pyrithione exhibited the highest cytotoxic activity against cancer cells. None of the tested antibiotics were cytotoxic to normal cells, whereas 8-hydroxyquinoline and sanguinarine exhibited selective antiproliferative activity against cancer cells. These findings indicate that 8-hydroxyquinoline alkaloids and metal-pyridine derivative complexes are chemical structures derived from plants with potential bioactive properties in terms of selective antibacterial and anticancer activities against diarrheagenic bacteria and intestinal cancer cells.
Highlights
The lack of an effective and safe antimicrobial therapy for diarrheagenic bacterial infections is a global health concern, especially in developing countries for children under the age of five years [1]
These findings indicate that 8-hydroxyquinoline alkaloids and metal-pyridine derivative complexes are chemical structures derived from plants with potential bioactive properties in terms of selective antibacterial and anticancer activities against diarrheagenic bacteria and intestinal cancer cells
8-hydroxyquinoline did not produce significant antibacterial activity against the pathogens (x-minimum inhibitory concentrations (MICs) = 224.4 ± 181), its growth-inhibitory activities were strong against E. faecalis (MIC = 4 μg/mL) and Listeria monocytogenes (MIC = 1 μg/mL)
Summary
The lack of an effective and safe antimicrobial therapy for diarrheagenic bacterial infections is a global health concern, especially in developing countries for children under the age of five years [1]. Mortality associated with bacterial diarrhea is low in developed countries, the increased incidence rates of inflammatory bowel disease and colorectal cancer have been attributed to gut dysbiosis that can result from chronic intestinal infections [2]. The applications of conventional antibiotics are limited, especially among children in developing countries, owing to high cost and increased risk of side effects including gut dysbiosis. There is a need to identify novel antimicrobial agents for infectious bacterial diarrhea to overcome the limitations of conventional antimicrobial drugs [3]
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