Synthesis, Characterization, Molecular Docking, Cell viability and Biological Activity of New Metronidazole Analogues against Cellulitis Causing Pathogens

Development of microbial resistance against commercial imidazoles intended present study to develop some new metronidazole analogues against cellulitis causing pathogens. In present study, N-(4-substituted benzylidene)-2-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)-acetohydrazide (2a-c) were synthesized by treating hydrazide derivative of metronidazole (1) with various aromatic aldehydes. The structures of synthesized compounds 2a-c were characterized using FT-IR, 1H NMR, 13C NMR and mass spectrometric data. The synthesized compounds 2a-c were evaluated for their inhibitory potential against cellulitis triggering bacteria S. aureus, E. coli and cell viability profile using MTT assay. Among compounds 2a-c, compound 2c incorporated with high electronegative group, exhibited maximum inhibitory potential against cellulitis triggering pathogens. This potential was also supported by the docking data of compounds 2c against glucosamine-6-phosphate (2VF5). The significant antibacterial potential of compounds 2a-c against S. aureus and E. coli, high cell viability against HEK 293 cells (more than 75%) and high docking score of compounds with 2VF5 supports their potential application in cellulitis treatment. However, the synthesized compounds should be further evaluated for their in vivo preclinical significance.