Synthesis, antimicrobial evaluation, and docking studies of new series Pyrazolone, Pyrimidine, Thiazine, and Pyranone derivatives bearing a Sulfonamide moiety using ultrasound irradiation

Abstract

This study presents a green chemistry approach to synthesizing new heterocyclic compounds with sulfadiazine moiety using ultrasound techniques. Diazotization of sulfadiazine (1) that results in the formation of diazonium salt(1a)followed by coupling of the latter with active methylene compounds leads to hydrazine derivative (2a-d). Heterocyclization of compounds(2a-d) with hydrazine and phenyl hydrazine gives to a series of pyrazole derivatives (3a-d) and (4a-d) under ultrasound irradiation. Subsequently, the pyrimidine derivatives (5a-d) and thiazine derivatives (6a-d) were synthesized upon treatment of hydrazone compounds (2a-d) with urea and thiourea under ultrasound irradiation. Additionally, pyran derivatives 8 and 10 were synthesized by combining reactions 2a and 2c with acetylacetone under ultrasonic irradiation at 60 °C. The chemical structures of the produced compounds were determined using 1H, 13C NMR, and FT-IR spectroscopic techniques. These compounds displayed moderate to good antimicrobial effects on human-pathogenic bacteria types, like Escherichia coli and Staphylococcus aureus, and on fungal types, such as C. albicans, which was determined through the broth microdilution technique. Molecular docking studies were then employed to demonstrate the active sites and the binding affinity of the products to the target proteins or receptors in S. aureus (PDB ID Code: 1HSK).