Synthesis and Polymerization of Some New Derivatives of Cefalexin Drug and Evaluating Its Antimicrobial Activities

Abstract

The primary amino group of cefalexin was condensed with selected aldehydes, which contain electron-donating and electron-withdrawing substituents, in ethanol under reflux conditions for 6–8 h in the presence of glacial acetic acid as a catalyst, to give a series of cefalexin Schiff bases (W1–W5; 55–82%). These Schiff bases were then polymerized with chitosan to give novel polymeric derivatives (W6–W10). FT-IR and ¹H-NMR spectroscopy were used to identify all the compounds, NH₂ bands disappeared and the appearance of bands in the 1625-1678 cm-1 region and ¹H-NMR signals at δ 8.5-9.0 ppm confirmed Schiff base formation. The antimicrobial activity was examined against Staphylococcus aureus, Escherichia coli (disk-diffusion) and Candida albicans (cup-plate) using Cefalexin as standard. The compound W5 exhibited the most significant antibacterial activity with the largest inhibition zones of 22 mm and 20 mm against E. coli and S. aureus respectively and W3 exhibited the maximum antifungal activity with the largest inhibition zone of 10 mm against S. aureus. The lowest IC₅₀ was obtained with polymeric derivative W7 and was 44.36 µg/mL, which was closest to the ascorbic acid standard (33.87 µg/mL) using the DPPH assay. The ADME analysis in silico shows that the monomeric Schiff bases meet Lipinski's Rule of Five. The results show that the Schiff base formation and chitosan polymerization approach is an effective way to improve the antimicrobial and antioxidant activity of cefalexin.