Synthesis, structural characterization and antimicrobial activity of some new tosyl-spirothiazolidinones

In this study, a novel series of 4-methyl-N-[2,7,8-(non)substituted)-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl]benzene-1-sulfonamides (3a-g, 4), bearing benzenesulfonamide and spirothiazolidinone scaffolds, have been synthesized. The target compounds were prepared in two steps starting from the p-toluenesulfonyl hydrazide (1). The 4-methyl-N-[3,4-(non)substitutedcyclohexylidene]benzene-1-sulfono hydrazide derivatives (2a-g), which were used as intermediate products, were obtained from the reaction of p-toluenesulfonyl hydrazide (1) with appropriate cyclic ketones. The spirothiazolidinone compounds (3a-g, 4) were synthesized by the cyclization of the intermediate hydrazones (2a-g) with thioglycolic acid/thiolactic acid. Compounds 3a-g and 4 were characterized by elemental analysis, UV, IR, 1H-NMR, 13C-NMR (APT), HSQC, HMBC and ESI-MS spectroscopic methods and their structures were confirmed. The antibacterial and antifungal activity of the new spirothiazolidinone compounds (3a-g, 4) were screened in vitro against Staphylococcus aureus ATCC 29213, Staphylococcus epidermidis ATCC 12228, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 14153, Candida albicans ATCC 1023, Candida. parapsilosis ATCC 22019 and Candida tropicalis ATCC 750. Their antimycobacterial activity was also tested in vitro against M. tuberculosis H37Rv ATCC 27294 (drug-sensitive strain), M. tuberculosis H37Rv ATCC 35822 (isoniazid-resistant strain), M. tuberculosis (isoniazid and rifampin-resistant strain, clinical isolate), M. tuberculosis (drug-sensitive strain, clinical isolate).