Design and Synthesis of a New Class of Pyridine-Based -Sulfonamides Exhibiting Antiviral, Antimicrobial, and Enzyme Inhibition Characteristics.

A new strategy for designing and assembling a novel class of functionalized pyridine-based benzothiazole and benzimidazole incorporating sulfonamide moieties was developed. The synthesis was carried out by reacting -cyanoacetoarylsulfonylhydrazide with various electrophiles such as 2-(benzo[]thiazol-2-yl)-3,3-bis(alkylthio)acrylonitriles and 2-(benzo[]imidazol-2-yl)-3,3-bis(methylthio)-acrylonitriles, as well as 2-ethoxyl acrylonitrile derivatives. The synthesized compounds were tested for their antiviral and antimicrobial potency. Two of the synthesized compounds, and , showed more than 50% viral reduction against HSV-1 and CBV4, with significant IC and CC values. The two potent compounds and have also shown inhibitory activity against Hsp90α protein with IC values of 10.24 and 4.48 μg/mL, respectively. A combination of and with acyclovir has led to IC values that are lower than that of acyclovir alone. Molecular modeling studies were used to identify the interactions between the and compounds and the active site of Hsp90α enzyme. The antimicrobial investigation of the new compounds has also shown that and exhibited a higher inhibition zone (IZ) than sulfadiazine and gentamicin against whereas showed higher IZ than ampicillin against . According to the enzyme assay study on dihydrofolate reductase, was shown to be the most potent compound among all examined compounds.