Synthesis of novel N-alkyl-2-(3,5-dimethyl-1,1-dioxido-2H-1,2,6-thiadiazin-4-yl)benzamides as potential antimicrobial agents

Abstract

Abstract Background/aims Derivatives of sulfamides have attracted interest in recent years as both acyclic and cyclic compounds exhibit a broad spectrum of physiological activities.1a–b 1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives exhibits antispasmodic activity,2 and are also proposed for the treatment of rheumatoid arthritis.3 Various 1,2,5-thiadiazolidine 1,1-dioxides analogues containing an indole substituent at position two are used for the treatment of migraines,4 and also inhibit human leucocyte elastase enzyme and cathepsin G.5 Thus we report the facile synthesis, characterization and biological evaluation of novel N -alkyl-2-(3,5-dimethyl-1,1-dioxido-2H-1,2,6-thiadiazin-4-yl)benzamides having novel substitution groups at the fourth position of the 1,2,6-thiadiazine ring. Methods The synthesis of novel potential antimicrobial agents of N -alkyl-2-(3,5-dimethyl-1,1-dioxido-2H-1,2,6- thiadiazin-4-yl)benzamides ( 2a–j ) were achieved by the reaction of 2-(3,5-dimethyl-1,1-dioxido-2H- 1,2,6-thiadiazin-4-yl)benzoic acid (1) with various aromatic and aliphatic amines using carbonyldiimidazole as a coupling agent. The products have been characterized by 1 H NMR, mass spectrometry and elemental analysis. Antimicrobial studies of the synthesized compounds show promising activity as potential antibacterial but not antifungal agents. Results All of the compounds demonstrated activity against the bacterial strains. In particular, this family of molecules was more active against the Gram-positive species Staphylococcus aureus and Bacillus subtilis than the Gram-negative Escherichia coli and Pseudomonas aeruginosa . The best results were achieved with molecules that had a cyclic aliphatic group i.e. 2c , 2e and 2g . Conclusion The results of novel N -alkyl-2-(3,5-dimethyl-1,1-dioxido-2H-1,2,6-thiadiazin-4-yl)benzamide derivatives preliminary bioassays indicate that a number of these molecules exhibit antibacterial activities against Gram-positive bacteria that are comparable to commercially available drugs. The modification of the heterocyclic ring of the parent compound offers a promising prospect and more active analogues are expected to be found.