title: Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives.
abstract: A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1-9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10-18. These were converted to the dibromo compounds 19-27 through reaction with bromine in glacial acetic acid. Compounds 19-27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28-72. Compounds 28-72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-positive bacteria Bacillus subtilis and Staphylococcous aureus. The range of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was 25-600 µg/mL, though some of the MIC and MBC concentrations were high, indicating weak activity. Structure activity relationship studies revealed that the compounds with a hydrogen atom or an ethyl group on the nitrogen of the thiazine ring exerted antibacterial activity against Gram-positive bacteria. The results also showed that the compounds where the benzene ring of the benzoyl moiety contained a methyl group or a chlorine or bromine atom in the para position showed higher antimicrobial activity. Similar influences were identified where either a bromine or chlorine atom was in the meta position.
authors.affiliation: School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK. chandanipatel21@hotmail.com.
authors.forename: Chandani
authors.initials: C
authors.lastname: Patel
authors.affiliation: School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK. j.p.bassin@herts.ac.uk.
authors.forename: Jatinder P
authors.initials: JP
authors.lastname: Bassin
authors.affiliation: School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK. m.scott6@herts.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Scott
authors.affiliation: EPSRC UK National Mass Spectrometry Facility, Institute of Mass Spectrometry, Swansea University Medical School, Swansea SA2 8PP, UK. mscentre@swansea.ac.uk.
authors.forename: Jenna
authors.initials: J
authors.lastname: Flye
authors.affiliation: EPSRC UK National Mass Spectrometry Facility, Institute of Mass Spectrometry, Swansea University Medical School, Swansea SA2 8PP, UK. a.p.hunter@swansea.ac.uk.
authors.forename: Ann P
authors.initials: AP
authors.lastname: Hunter
authors.affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Clifton, Nottingham NG11 8NS, UK. lee.martin@ntu.ac.uk.
authors.forename: Lee
authors.initials: L
authors.lastname: Martin
authors.affiliation: School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK. m.goyal@herts.ac.uk.
authors.forename: Madhu
authors.initials: M
authors.lastname: Goyal
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000606503:1,2-benzothiazine; D000890:Anti-Infective Agents; D013843:Thiazines
keywords: 1,2-benzothiazines; Bacillus subtilis; Proteus vulgaris; Salmonella typhimurium; Staphylococcous aureus; chalcones