4H-1,4-benzothiazine, dihydro-1,4-benzothiazinones and 2-amino-5-fluorobenzenethiol derivatives: design, synthesis and in vitro antimicrobial screening.

Domenico Armenise, Marilena Muraglia, Marco Antonio Florio, Nicolino De Laurentis, Antonio Rosato, Antonio Carrieri, Filomena Corbo, Carlo Franchini

Index: Arch. Pharm. (Weinheim) 345(5) , 407-16, (2012)

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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.Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.