Synthesis and Structural Characterization of Ampicillin-Derived Schiff Bases with Enhanced Biological Potential

Mr.Rajashekhar N, Ms.Mounashree U, Ms.Nanditha B R.

The growing challenge of antimicrobial resistance necessitates the structural modification of existing antibiotics to improve their efficacy. Ampicillin, a widely used semi-synthetic β-lactam antibiotic, exhibits broad-spectrum activity but is vulnerable to β-lactamase degradation. Schiff base formation offers a promising approach to enhance its stability and antimicrobial potential. The present study focuses on the synthesis, characterization, and biological evaluation of Schiff base derivatives of ampicillin using selected ketones. Ampicillin was reacted with acetophenone, benzoin, and anthrone under microwave-assisted conditions in methanol with concentrated hydrochloric acid as a catalyst, yielding three derivatives: APAC, APB, and APA. Product formation was monitored using TLC. The synthesized compounds were structurally characterized through FT-IR, ¹H-NMR, mass spectroscopy, and melting point analysis. FT-IR spectra confirmed the presence of characteristic azomethine (C=N), carbonyl (C=O), hydroxyl, and amide groups. ¹H-NMR data validated the proton environment of APAC, while the mass spectrum of APA showed a molecular ion peak at m/z 525, consistent with its molecular formula. Biological screening of selected derivatives demonstrated improved antimicrobial activity compared to ampicillin. Physicochemical parameters, including C log P, drug-likeness, and drug score, supported the compounds’ suitability as drug candidates. Overall, the synthesized Schiff bases showed promising potential as enhanced antibacterial agents.

Keywords: Ampicillin, Antibacterial activity, FT-IR, ¹H-NMR, Ketone derivatives, Mass spectrometry, Schiff bases.