Evaluation of 1,2-Benzothiazine 1,1-Dioxide Derivatives In Vitro Activity towards Clinical-Relevant Microorganisms and Fibroblasts

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-positiveStaphylococcus aureusandEnterococcus faecalisstrains was higher than antimicrobial activity of DMSO solvent, which possesses antimicrobial activity itself. Gram-negativeP. aeruginosa,E. coliandK. pneumoniaehave shown susceptibility only to compounds3e,7iand7l. None of tested compounds was effective againstC. albicans.Compound6ghas demonstrated the strongest antimicrobial potency (MIC = 0.00975 mg/mL) among compounds of series6. Compounds of series7, namely7d,7f,7ghad the lowest minimum inhibitory concentration (MIC). Compound7fdisplayed also the lowest cytotoxic effect against fibroblast cell line among series7compounds. 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.