Antibacterial activity and DNA gyrase inhibitory potency of some novel pyrazolo[1,5- <i>a</i> ]pyrimidine-based thiazolidin-4-one hybrids linked to aryl units

The rising antimicrobial resistance leads to the need to develop new antimicrobial scaffolds. DNA gyrase is a vital, bacteria-specific enzyme, a prime target for the discovery of new antibiotics. The potential anti-DNA gyrase potency of some pyrazolo[1,5-a]pyrimidine-based 2-arylthiazolidin-4-ones 1 was examined. These products were obtained herein, in 77-94% yields, by reacting a mixture of the proper amines, benzaldehydes, and thioglycolic acid in refluxing ethanol for 5–6 h containing 20 mol% para-toluenesulfonic acid. Hybrids 1d and 1k, attached to 4-nitrophenyl units at thiazolidinone-C2, displayed comparable potency to ciprofloxacin with MIC/MBC of 1.77/3.53 and 1.39/2.79 µM, respectively, against S. aureus and MIC/MBC of 2.82/5.65 and 2.23/4.45 µM, respectively, against E. faecalis and P. aeruginosa. 1d and 1k demonstrated promising anti-MRSA potency with MIC/MBC of 3.53/14.13 and 2.79/11.15 µM, respectively, and significant S. aureus DNA gyrase inhibitory activity, with IC50 of 1.78 and 1.52 μM, respectively.