Schiff Base Mediated Synthesis of Novel Imidazolidine-4-One Derivatives for Potential Antimicrobial and Anthelmintic Activities

This study focuses on developing novel antimicrobials to combat drug-resistant pathogens, addressing compounds failing clinical trials due to inadequate physicochemical properties. Sixteen imidazolidine-4-one derivatives were synthesized by extensive evaluation using molecular docking, absorption, distribution, metabolism, excretion (ADME) predictions, and antimicrobial testing. Molecular docking studies conducted with Schrödinger's Glide revealed that compounds S4 and G8 exhibited superior docking scores of −7.839 and −7.776, respectively. The G series outperformed the S series in scores. ADME analysis confirmed all compounds adhered to Lipinski's rule of five. In addition, IR and NMR provided details about the structure of the compounds. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus, and Candida albicans, with compounds G2 and S2 showing exceptional minimum inhibitory concentration (MIC) values of 6.25 μg/mL against E. coli. S2 also demonstrated impressive activity against S. aureus (MIC 3.12 μg/mL), and S4 exhibited potent activity against C. albicans (MIC 0.8 μg/mL) than fluconazole (1.6 μg/mL). Additionally, antihelmintic activity was evaluated, with G1, G3, G8, S2, S4, S7, and S8 showing effective paralysis and death time 20 min and below at 50 mg/mL concentration. These results underscore the potential of new imidazolidine-4-one derivatives as suitable sources to develop a drug candidate to treat resistant infections.