Synthesis, in vitro Antimicrobial Evaluation, Molecular Docking and Phytotoxicity Profiling of N-(Substituted benzylidene)-5-(substituted phenyl)-1,3,4-oxadiazol-2-amines

A series of N-(substituted benzylidene)-5-(substituted phenyl)-1,3,4-oxadiazol-2-amines (2AC07-2AC13) was synthesized through a three-step sequence involving hydrazone formation, oxidative cyclization to the 1,3,4-oxadiazol-2-amine scaffold and final Schiff-base condensation. The products were characterized using FT-IR, 1H and 13C NMR and HRMS. In vitro antimicrobial screening was conducted against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacterial strains and fungal strains (Candida albicans, Aspergillus niger and Trichoderma sp.) using the agar well diffusion method, with ampicillin and fluconazole as respective reference standards. The series exhibited selective antimicrobial activity however compound 2AC11 displayed concentration-dependent antibacterial activity against B. subtilis and P. aeruginosa while compounds 2AC07-2AC09 demonstrated antifungal activity against all three tested fungal strains. Compound 2AC09 showed the highest antifungal profile against A. niger, Trichoderma sp. and C. albicans at 100 µg mL–1 and was selected for molecular docking against A. niger EstA (PDB: 1UKC) and C. albicans CYP51 (PDB: 5TZ1). Their phytotoxic effects were assessed in a Petri-dish assay using tomato (Solanum lycopersicum) seeds exposed to 10, 50, 100 and 300 ppm. The germination speed index (GSI), root elongation and shoot elongation were normalized against the water control and integrated into a phytotoxicity index (PTI). The biological activity profile identifies compound 2AC11 as a potential selective antibacterial candidate and compound 2AC09 as a promising antifungal scaffold for further structural modification and optimization.