Design, synthesis, characterization, and biological evaluation of novel pyrazine-1,3,4-oxadiazole/[1,2,4] triazolo[3,4-b][1,3,4]thiadiazine hybrids as potent antimycobacterial agents

Abstract

In this study, we present novel pyrazine-1,3,4-oxadiazole hybrids (T1-T9) and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives (T10-T18), which possess remarkable antimicrobial activity. These compounds have been meticulously scrutinized for their efficacy in combatting the M. tuberculosis H37Rv strain. Three compounds T7, T8, and T17 showed promising antitubercular activity with MIC of 1.56 µg/mL. The target compounds are also evaluated for their antibacterial activity against S. aureus, S. mutans, E. coli, and S. Typhi, and antifungal activity against A. niger. Most of the compounds showed significant antibacterial and antifungal activity. All the active compounds exhibited very low toxicity and none of the active compounds were toxic to the normal cells. To deepen our understanding of these compounds, an in-silico ADME, and molecular docking analysis against the DprE1 enzyme were conducted, followed by DFT studies to shed some light on their electronic properties, and enhance our grasp of their pharmacological potential. © 2024 Elsevier B.V.