Ultrasound-assisted synthesis and antibacterial activity of novel 1,3,4-thiadiazole-1H-pyrazol-4-yl-thiazolidin-4-one derivatives

We report an efficient multicomponent method for the synthesis of biologically active 1,3,4-thiadiazole-1H-pyrazol-4-yl-thiazolidin-4-one hybrids from the reaction of pyrazole-4-carbaldehyde, 5-(substituted phenyl)-1,3,4-thiadiazol-2-amines, and 2-mercaptoacetic acid in ethanol under ultrasound irradiation. Reactions gave excellent yields (91-97%) of desired products in short times (55-65 min) at 50 degrees C. All the twelve new thiazolidin-4-one derivatives were fully characterized by spectroscopic techniques and were screened for their antibacterial activity. Among the screened hybrids, derivatives with 4-nitro and 3-nitro groups substituted on the phenyl ring showed fourfold (MBC = 156.3 mu g/cm(3)) and twofold (MBC = 312.5 mu g/cm(3)) stronger potency against Pseudomonas aeruginosa strain as compared to the standard ciprofloxacin. SAR studies revealed the importance of the functional groups on the phenyl ring of 1,3,4-thiadiazol-2-amine moiety for varying bacterial activity. The electron-withdrawing (NO2) group at para- and meta-position played a significant role in enhancing the antibacterial activity. The prominent features of the described protocol are excellent yields, green protocol, catalyst-free, high atom economy (94%), and excellent carbon efficiency (98%).