Synthesis, Spectral Characterization, and Antibacterial Evaluation of Citric Acid–Based Drug Modifications

This study describes the synthesis of novel drug modifications produced through the interaction of citric acid with selected pharmaceuticals, namely paracetamol, ciprofloxacin, theophylline, and cephalexin, yielding four derivatives (T1–T4). The synthesized compounds were characterized using FTIR, 1H NMR, and 13C NMR spectroscopy. Their physicochemical properties, including solubility, color, and melting point, were systematically examined. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) using inhibition zone measurements, and the results were compared with those of the corresponding parent drugs. The results revealed that compound T4 exhibited enhanced antibacterial activity against both bacterial strains, showing inhibition zones of 26 mm against S. aureus and 25 mm against E. coli, exceeding those of cephalexin (17 mm and 20 mm, respectively). Compound T2 displayed antibacterial activity comparable to ciprofloxacin, with inhibition zones of 38 mm (S. aureus) and 35 mm (E. coli), relative to 39 mm for the parent drug against both strains. In contrast, compounds T1 and T3 showed reduced antibacterial effectiveness compared to paracetamol and theophylline, respectively, as reflected by smaller inhibition zones against both microorganisms. In addition, spectrophotometric analysis indicated that all synthesized compounds exhibited strong ultraviolet absorption in the 260–280 nm range. Overall, the findings identify T4 as the most promising derivative, demonstrating improved antibacterial performance relative to its parent drug and highlighting the potential of citric acid–based modifications in pharmaceutical development.