ABSTRACT
The global concern related with growing number of bacterial pathogens, resistant to numerous antibiotics, prone scientific environment to search for new antimicrobials. Antiseptics appear to be suitable candidates as adjunctive agents to antibiotics or alternative local treatment option aiming to prevent and treat infections. 1,2-benzothiazines are considered one the most promising of them. In this research twenty 1,2-benzothiazine 1,1-dioxide derivatives were scrutinized with regard to their biological activity. Three of them are new. For evaluation of compounds' activity against microbial pathogens, disk diffusion method and serial microdilution method was applied. To establish the cytotoxicity profile of tested 1,2-benzothiazines 1,1-dioxides derivatives, the cytotoxicity assay using fibroblasts L292 was performed. Antimicrobial activity of all tested compounds against Gram-positive Staphylococcus aureus and Enterococcus faecalis strains was higher than antimicrobial activity of DMSO solvent, which possesses antimicrobial activity itself. Gram-negative P. aeruginosa, E. coli and K. pneumoniae have shown susceptibility only to compounds 3e, 7i and 7l. None of tested compounds was effective against C. albicans. Compound 6g has demonstrated the strongest antimicrobial potency (MIC = 0.00975 mg/mL) among compounds of series 6. Compounds of series 7, namely 7d, 7f, 7g had the lowest minimum inhibitory concentration (MIC). Compound 7f displayed also the lowest cytotoxic effect against fibroblast cell line among series 7 compounds. All tested derivatives displayed lower MIC against Gram-positive bacteria than commercially applied antiseptic, povidone iodine, which MIC value range for tested Gram-positive bacteria was 1.56-6.25 mg/mL.
Subject(s)
Anti-Infective Agents/chemistry , Oxides/chemistry , Thiazines/chemistry , Animals , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Candida albicans/drug effects , Cell Line , Cell Survival/drug effects , Crystallography, X-Ray , Fibroblasts/cytology , Fibroblasts/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Mice , Microbial Sensitivity Tests , Molecular Conformation , Structure-Activity Relationship , Thiazines/chemical synthesis , Thiazines/pharmacologyABSTRACT
The gut microbiota acts as a real organ. It exerts important metabolic functions, and regulates the inflammatory response by stimulating the immune system. Gut microbial imbalance (dysbiosis) has been linked to important human diseases and inflammation-related disorders. The symbiotic interactions between resident microorganisms and the gastrointestinal tract significantly contribute to maintaining gut homeostasis. The present review summarizes our knowledge regarding the impact of different antibiotics causing such long-term consequences as decreased microbial diversity, modulation of the Bacteroidetes/Firmicutes ratio, Clostridium difficile overgrowth, and increased expansion of the opportunistic pathogens Salmonella typhimurium, Escherichia spp., and Klebsiella spp. Also, food additives, such as emulsifiers and artificial sweeteners, which are meant to reduce the risk of obesity and diabetes, may actually increase the risk of diseases due to microbial alterations. On the other hand, dietary components such as polyphenols, omega-3 acids or curcumin may positively affect gut microbiota composition.
