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

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 8μg/mL and the fungi panel with MIC values between 2 and 8μg/mL. These results may prove useful in the design of a novel pool of antimicrobial agents. Benzothiazine, benzothiazinones and amino-5- fluorobenzenethiol derivatives were prepared to identify compounds with a potent antimicrobial profile. All obtained compounds were screened for in vitro antibacterial activity against Gram-positive and Gram-negative bacteria strains and a fungi panel. The most active compounds, substituted-2-amino-5- fluorobenzenethiol, exhibited an interesting antibacterial activity with MIC values between 2 and 8μg/mL against both Gram-positive bacteria and the fungi panel. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.