Synthesis and In vitro Screening of Pyrazine-2-Carbohydrazide Derivatives as Potential Antimicrobial Agents

Abstract

Herein, we report the design of a new set of pyrazine-2-carbohydrazide derivatives (T1–T20) and in silico investigations to evaluate their inhibition activity against the enzyme, decaprenylphosphoryl-[Formula: see text]-D-ribose 2′-epimerase (DprE1). The derivatives interact with the Cys387 residue of the enzyme’s active site through hydrogen bonds. Further, we synthesized these compounds and evaluated their efficacy against the M. tuberculosis H37Rv strain. Compounds T16 and T19 displayed promising antitubercular activity, boasting a minimal inhibitory concentration of 1.56 [Formula: see text]g/mL. Furthermore, we assessed the antibacterial activity of these compounds against a range of pathogens, including S. aureus, S. mutans, E. coli and [Formula: see text]Typhi. Additionally, we evaluated their antifungal potency against A. niger. Notably, compounds T4, T8, T9, T16 and T19 exhibited noteworthy antibacterial activity against tested bacterial strains. Compounds T4, T9, T16, T17, T18 and T19 showed significant inhibition activity against A. niger. Importantly, all active compounds demonstrated low cytotoxicity, with IC50 values exceeding 300 [Formula: see text]M, ensuring no harm to normal cells. To gain a deeper understanding of these compounds, we conducted in silico investigations to evaluate their pharmacokinetics and pharmacochemical properties. Additionally, we employed DFT studies to explore the electronic characteristics of these compounds, providing valuable insights into their potential applications in the pharmaceutical field.