Synthesis, Characterization, and Antibacterial Activity of Indole Derivatives Containing Amidothiourea With...

A series of novel indole-based amidothiourea-1,3,4-oxadiazole derivatives 8a-o were synthesized and evaluated against four pathogenic Vibrio strains by the agar well diffusion method and minimum inhibitory concentration (MIC) assays. Most of the target compounds exhibited potent antibacterial efficacy, among which compound 8f showed the strongest activity against Vibrio harveyi with an MIC value of 0.0019 mg/mL, approximately 8-fold more potent than the positive control streptomycin sulfate (MIC = 0.0156 mg/mL). Structure-activity relationship (SAR) analysis indicated that the influence of substituent position appeared to depend on the bacterial strain and the nature of the substituent, with para-substituted moderate electron-withdrawing groups generally demonstrating favorable activity in certain strains. Notably, compound 8d displayed broad-spectrum inhibitory effects against all four tested strains. To further clarify the antibacterial mechanism, molecular docking simulations were carried out with V. harveyi hemolysin (VHH) as the potential target. Compound 8f exhibited strong binding affinity (ΔG = -11.38 kcal/mol) and formed stable hydrogen bonds and hydrophobic interactions within the active pocket of VHH, which was consistent with its superior in vitro antibacterial performance. These results indicate that the indole-based amidothiourea-1,3,4-oxadiazole scaffold may represent a promising lead structure for the design and development of novel anti-Vibrio agents targeting VHH hemolysin.