In this article, a series of benzothiazole-bearing N-sulfonamide 2-pyridone derivatives were synthesized via the reaction of benzothiazole sulfonylhydrazide with sodium salts of both (hydroxymethylene) cycloalkanones and unsaturated ketones, as well as ethoxymethylene derivatives. The structures of the resultant compounds were confirmed using IR, ¹H NMR, ¹³C NMR, ¹H–¹H correlation spectroscopy (COSY), ¹H–¹³C heteronuclear multiple bond coherence (HMBC), and ¹H–¹³C heteronuclear multiple quantum coherence (HSQC) spectral analysis and elemental analysis. The newly synthesized compounds were evaluated in vitro for their antiviral activities against the HSV-1, HAV HM175, HCVcc genotype 4, CBV4, and HAdV7 viruses. Additionally, the compounds were examined for their cytotoxic effect on five normal cell lines. It was observed that five compounds were found to possess viral reduction of 50% or more against CBV4 with significant IC₅₀, CC₅₀, and SI values. In the case of HSV-1 and HAV HM175 viruses, three compounds have shown more than 50% reduction, while in the case of HCVcc genotype 4 and HAdV7 viruses, only two compounds demonstrated more than 50% reduction. Furthermore, the physicochemical properties of the most active compounds were evaluated. The two most potent compounds against HSV-1 virus, 7e and 13a, were evaluated for their inhibitory activity against USP7. Docking studies using Molecular Operating Environment (MOE) were used to identify the interactions between 7e and 13a compounds and the active site of the USP7 enzyme.

By Rasha A. Azzam, Heba A. Elboshi, and Galal H. Elgemeie