A pyrazinamide-benzenesulfonohydrazide hybrid N'-(phenylsulfonyl)pyrazine-2-carbohydrazonamide: Experimental and theoretical insights.

A pyrazinamide-benzenesulfonohydrazide hybrid N' -(phenylsulfonyl)pyrazine-2-carbohydrazonamide (1), which was studied by physical measurements and computational tools, is reported. Compound 1 was synthesized using a metallic Na-assisted interaction of 2-cyanopyrazine with benzenesulfonylhydrazine in dry methanol. Our newly developed synthetic approach allowed to obtain the title compound witht the yield of 74%, which is more than twice higher in comparison to the previously reported synthesis using pyrazine-2-carbohydrazonamide and benzenesulfonyl chloride. Molecules of the title compound are linked via N–H⋯O, C–H⋯Ph, S=O⋯2-pyrazine and π⋯π interactions. As it was found by the Hirshfeld surface analysis, molecules of 1 interact through H⋯X (X = H, C, N and O) contacts. Electronic properties of 1 were revealed using the Density Functional Theory (DFT) computations. 1 was expected to be a fourth-class toxicity, and it does not penetrate the blood-brain barrier, while can potentially be absorbed by the gastrointestinal tract. It was predicted that compound 1 , which demonstrated the strongest activity against PLpro, Nsp3_range 207–379 MES and Nsp16_SAM site, are of interest to suppress activity of the SARS-CoV-2 proteins. Although the K i value is slightly higher, the ligand efficiency scores for complex PLpro– 1 were found to be characteristic for a Hit. We report on a novel pyrazinamide-benzenesulfonohydrazide hybrid N' -(phenylsulfonyl)pyrazine-2-carbohydrazonamide (1), which was studied by physical measurements and computational tools. [Display omitted] • N' -(phenylsulfonyl)pyrazine-2-carbohydrazonamide (1) is reported. • Crystal structure of 1 was studied in detail. • Electronic properties of 1 were revealed using the DFT computations. • 1 was probed in silico as a potential inhibitor of the SARS-CoV-2 proteins. [ABSTRACT FROM AUTHOR]