title: 4H-1,4-benzothiazine, dihydro-1,4-benzothiazinones and 2-amino-5-fluorobenzenethiol derivatives: design, synthesis and in vitro antimicrobial screening.
abstract: As part of our studies focused on the design and synthesis of new antimicrobial agents a series of 7-fluoro-3,4-dihydro-2H-1,4-benzothiazine derivatives (4a-4f, 4h) and 7-fluoro-2H-1,4-benzothiazin-3(4H)-one analogues (4j-4o) were synthesized and evaluated for their in vitro inhibitory activity against a representative panel of Gram-positive and Gram-negative bacteria strains and also toward selected fungi species. These compounds were prepared in one step from chloro-substituted-2-amino-5-fluorobenzenethiol 6a-6c. The biological screening identified in compounds 4a, 4j and 4l the most promising results of both series showing an interesting antimicrobial activity. Our antibiotic investigation was also completed by testing the key intermediates 6a-6c. Surprisingly, 6a-6c emerged as the compounds exhibiting the highest antimicrobial activity by possessing a remarkable antibacterial effect against the Gram-positive strains with MIC (minimal inhibitory concentration) values between 2 and 8 µg/mL and the fungi panel with MIC values between 2 and 8 µg/mL. These results may prove useful in the design of a novel pool of antimicrobial agents.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Bari, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Armenise
authors.forename: Marilena
authors.initials: M
authors.lastname: Muraglia
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Florio
authors.forename: Nicolino
authors.initials: N
authors.lastname: De Laurentis
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrieri
authors.forename: Filomena
authors.initials: F
authors.lastname: Corbo
authors.forename: Carlo
authors.initials: C
authors.lastname: Franchini
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010636:Phenols / Q000138:chemical synthesis / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C446962:1,4-benzothiazine; D000890:Anti-Infective Agents; D010636:Phenols; D013438:Sulfhydryl Compounds; D013843:Thiazines; C042983:thiophenol