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

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.

Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach

“…All the synthesized derivatives were well characterized with 1 H-NMR, 13 C-NMR, and MS spectroscopic techniques. In the 1 H-NMR spectra, the methylene (CH 2 ) protons appeared as a singlet at 3.95-4.20 ppm and the observation was consistent with literature values of similar compounds [46,49]. The methyl protons (CH 3 ) and methoxy protons appeared as singlets at 1.96-2.17 and 3.64-3.86 ppm, respectively.…”

“…The precursors, 3-(benzoyl/4-bromobenzoyl)-1,2-benzothazines 9a,b, were synthesized via reported methods involving Gabriel-Colman rearrangement [46,47]. Later on, 3-(benzoyl/4-bromobenzoyl)-1,2-benzothazines 9a,b were treated with a library of 2-bromo-N-arylacetamides 10a-m (synthesized as described previously [48]) in the presence of a potassium carbonate base in a DMF solvent.…”

“…The dried N-alkylated saccharin derivatives (8a,b) (1.0 mmol) were refluxed with sodium methoxide (270 mg, 5.0 mmols) in dry methanol for 30 min. The mixture was cooled and treated with 15% cold HCl to get the 3-(benzoyl/4-bromobenzoyl)-1,2-benzothiazines (9a,b) [46,47] in good isolated yields (given below). The products were also re-crystallized with methanol.…”

Antibiofilm and Antimicrobial-Enhancing Activity of Chelidonium majus and Corydalis cheilanthifolia Extracts against Multidrug-Resistant Helicobacter pylori

“…The normative neutral red cytotoxicity assay was performed for hepatic (HepG2; ATCC HB-8065, Manassas, VA, USA) and gastric (AGS; ATCC CRL-1739, Manassas, VA, USA) cell cultures treated with tested plant extracts (extracts from the underground parts of C. majus (A4/2) and the aerial parts of C. cheilanthifolia (A5/1)) [ 59 , 60 ]. Cells were seeded onto a 96-well microtitration plate at density of 2 × 10 4 cells per well in a high glucose DMEM culture medium (Dulbecco’s modified Eagle’s medium; Gibco, Paisley, Scotland, UK) or F-12 medium (Biowest LLC, Riverside, MO, USA) supplemented with 10% bovine serum (Gibco, Paisley, Scotland, UK) and antibiotics (penicillin 100 U/mL and streptomycin 0.1 mg/mL, both from Gibco, Paisley, Scotland, UK).…”

Identification of Cyclic Sulfonamides with an N-Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling

“…The 3-(3-methoxybenzoyl)-1,2-benzothazine 11 was synthesized according to the reported method [46,47], starting from the α-bromination of 3-methoxyacetophenone 8 with N-bromosuccinamide (NBS) [48] followed by a substitution reaction with sodium saccharin to get bezoisothiazolone 10. The base catalyzed Gabriel-Colman rearrangement [35,49] converted the bezoisothiazolone 10 into isomeric 3-(3-methoxybenzoyl)-1,2-benzothazine 11, which was coupled with a variety of 2-bromo-N-arylacetamides [50] under basic conditions (K 2 CO 3 ) in DMF. Dilution with water and then addition of cold dil.…”