Synthesis, Anti-mycobacterial activity, Molecular Docking and ADME analysis of spiroquinoxaline-1,2,4-oxadiazoles via [3+2] cycloaddition reaction under ultrasound irradiation

Abstract A convenient ultrasound methodology was employed to attain spiroquinoxaline-1,2,4-oxadiazoles via [3+2] cycloaddition of quinoxalineSchiff bases and aryl nitrile oxides at room temperature. This approach evades standard heating and column chromatography while producing high yields and lesser reaction times. The target compounds 3a-p were well characterized and their in vitro anti-mycobacterial activity (anti-TB) was evaluated. Among the screened compounds 3i has displayed promising activity against Mycobacterium tuberculosis cell line H37Rv with MIC value 0.78 µg/mL. However, three compounds ( 3f, 3h and 3o ) exhibited potent activity with MIC value 6.25 µg/mL. To further understand the binding interactions, the synthesized compounds were docked against the tuberculosisprotein 5OEQ using in silico molecular docking. Moreover, the utmost active compounds were additionally partitioned for their cytotoxicity against RAW 264.7 cell line, which revealed that the compounds 3f , 3h , 3i and 3o were less harmful to humans. Furthermore, the synthesized compounds were tested for ADME qualities, and the results suggest that this series is useful to produce innovative and potent anti-tubercular medicines in the future.