Synthesis, <i>in silico</i> and <i>in vitro</i> antimicrobial efficacy of some amidoxime-based benzimidazole and benzimidamide derivatives

Amidoximes are employed as building blocks to synthesise heterocyclic motifs with biological significance. They are very reactive and are used as prodrugs of amidine. This present study unveils the synthesis of amidoxime-based benzimidazole and benzimidamide motifs and evaluates their <i>in silico</i> and <i>in vitro</i> antimicrobial potential as future drug candidates. The compounds (2a, 2b, 4a-c) were synthesized using multi-step synthetic pathways. The synthesised compounds were characterised using physico-chemical examination, ¹H- and ¹³C-NMR, DEPT-135, and FT-IR spectroscopic analyses. The <i>in silico</i> antimicrobial potentials of the synthesized compounds were carried out against glucosamine-6-phosphate synthase of <i>E. coli</i> (PDB ID: 2VF5), and <i>N</i>-myristoyltransferase (NMT) of <i>C. albicans</i> (PDB ID: 1IYL), while the <i>in vitro</i> antimicrobial screening was investigated against selected bacteria and fungi. The <i>in silico</i> studies were carried out using predicted ADMET screening, molecular docking, MM-GBSA, induced-fit docking (IFD), and molecular dynamics (MD) simulation studies. Furthermore, the <i>in vitro</i> experimental validations were performed using the agar diffusion method and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole respectively. The predicted toxicity test of the compounds showed no significant risk, except for 4c, which showed high tumorigenic risk. Compounds 2b and 2a gave better binding energies; -8.0 kcal mol^-1 for 2VF5 and -11.7 kcal mol^-1 for 1IYL, respectively. The antimicrobial zone of inhibition and minimum inhibitory concentration values were 40 mm and 3.90 mg mL^-1 against <i>S. mutans</i>, then 42 mm and 1.90 mg mL^-1 against <i>C. albicans</i>. Potential antimicrobial drug candidates have been identified in this report and should be explored for future preclinical research.