Ligand-based design and synthesis of N'-Benzylidene-3,4-dimethoxybenzohydrazide derivatives as potential antimicrobial agents; evaluation by in vitro, in vivo, and in silico approaches with SAR studies.

Herein, a series of N'-benzylidene-3,4-dimethoxybenzohydrazide derivatives were designed and synthesised to target the multidrug efflux pump (MATE). The antibacterial activities were screened against S. aureus, Acinetobacter, S. typhi, E. coli, and P. aeruginosa, whereas their antifungal activities were screened against C. albicans. Compounds 4a, 4h, and 4i showed the most promising antibacterial and antifungal activities. Moreover, compounds 4h and 4i being the broader and superior members regarding their anti-microbial effects were selected to be further evaluated via in vivo testing using biochemical analysis and liver/kidney histological examination. Additionally, molecular docking was carried out to attain further deep insights into the synthesised compounds' binding modes. Also, ADMET studies were performed to investigate the physicochemical/pharmacokinetics features and toxicity parameters of the synthesised derivatives. Finally, a structure-antimicrobial activity relationship study was established to facilitate further structural modifications in the future. [ABSTRACT FROM AUTHOR]