Synthesis, Characterization and Biological Evaluation of Novel Saccharin–Thiadiazole Derivatives as Potential Antimicrobial Agen

A new series of saccharin–propane hybrid derivatives was successfully synthesized through a multistep synthetic pathway. Initially, substituted benzoic acid derivatives were reacted with thiosemicarbazide in the presence of phosphorus oxychloride (POCl₃) to yield 2-amino-5-(substituted phenyl)-1,3,4-thiadiazole intermediates, designated as L1–L3. Subsequently, these intermediates were treated with 1-chloro-3-bromopropane to afford the corresponding chloropropyl derivatives M1–M3. In the final step, nucleophilic substitution with sodium saccharin produced the desired saccharin-containing compounds S1–S3. The structures of the synthesized compounds were confirmed using Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance spectroscopy (^1H NMR and ^13C NMR). The antimicrobial potential of compounds S1–S3 was evaluated against three bacterial strains and the fungal strain Candida albicans. Antimicrobial activity was assessed using the agar diffusion technique, and the minimum inhibitory concentration (MIC) values were determined. Among the produced derivatives, substance S2 showed the best inhibitory action against Pseudomonas aeruginosa, while compounds S1, S2, and S3 revealed significant antimicrobial activities against the other examined bacteria. Also, MIC testing in nutritional broth media indicated that substance S2 has a minimum inhibitory concentration of 62.5 μg/mL with P. aeruginosa and 31.2 μg/mL with Candida albicans. The safety profile of substance S2 was further studied by EDTA-tube assay and blood agar hemolysis test. The results obtained showed that the substance was not found to be poisonous and it was biocompatible at high level within the measured concentration range of (1000,500, 250, 125, 62.5) μg/mL.