Design, Synthesis, and Biological Evaluation of Schiff Base and Azo Derivatives of Cefixime: Antibacterial, Antifungal, Antioxidant, ADMET, and Docking Studies

The development of new antibiotics is imperative due to the increasing resistance of bacteria to existing drugs. This study aimed to synthesize Schiff bases and azo derivatives of cefixime, a third-generation cephalosporin, and to evaluate their antimicrobial and antioxidant activities. The antibacterial activity of the synthesized compounds was assessed against Candida albicans and various Gram-positive and Gram-negative pathogens. Several derivatives exhibited potent antibacterial and antifungal activities, with compounds C6 and C9 demonstrating superior efficacy compared to standard antibiotics. Furthermore, molecular docking simulations revealed favorable interactions between these derivatives and beta-lactamase enzymes as well as penicillin-binding proteins, providing insights into their mechanism of action. Despite some limitations in bioavailability, the ADMET analysis clarified their pharmacokinetic profiles and confirmed their potential for systemic administration. These findings highlight the potential of cefixime-derived azo compounds and Schiff bases as novel strategies to overcome antibiotic resistance. Notably, compounds C9 and C6 differentiated themselves through enhanced antibacterial and antioxidant properties, making them promising candidates for further research, including preclinical and clinical evaluations following comprehensive pharmacological and therapeutic assessments.