Structural, medicinal, and toxicological study of cephalosporin degradation products: a DFT and in-silico approach

β-Lactam antibiotics like the Cephalosporins (CPS) continue in their application for several different infections caused by bacteria. The potential degradants of antibiotics, generated through different degradation pathways, may exhibit distinct kinetics, reactivity, and mechanisms, contributing to medicinal and toxicological features in biological system. Our study focused on a comprehensive in-silico analysis of CPS and its degradants. Molecular structures were optimized with density functional theory (DFT) by employing B3LYP/6-311G + + (d,p) basis sets, and their spectroscopic properties, like IR and UV–Vis spectra, were simulated to understand their electronic and vibrational properties. Molecular docking & dynamics simulation studies conducted against Penicillin Binding Protein 4 (ID: 3A3F) to assess binding affinities, interaction modes, and structural stability or flexibility. Furthermore, ADMET and PASS predictions evaluated toxicity and biological activity. Here, C4 is the most chemically reactive degradative degradant of Cephalosporins, with the lowest HOMO–LUMO gap, hardness, and softness due to the CF3 group at the bridging carbon. Molecular docking studies revealed that four Cephalosporin degradants (C4, C7, C8, and C10) bind strongly to the target protein, with C4 having the highest binding affinity of -7.0 kcal/mol. Following a 100 ns dynamics simulation, the drugs remained tightly bound to the binding site of the receptor protein, showing significant interactions with shorter distances among the new degradants. All compounds met Lipinski's Rule, confirming drug-likeness, PASS predicted strong bioactivities, and ADMET demonstrated CYP2C9/hERG inhibition. This study highlights the biochemical and toxicological effects of CPS degradants on biological systems.