Ferrocenyl bioconjugates of ampicillin and 6-aminopenicillinic acid – Synthesis, electrochemistry and biological activity

Abstract

We report on the synthesis of ferrocenyl–ampicillin and ferrocenyl–6-aminopenicillinic acid bioconjugates. Title compounds were characterized by 1H NMR, IR, MS and elemental analysis. These novel ferrocenyl-antibiotic conjugates were also investigated by cyclic voltammetry (CV). Ferrocenyl–ampicillin complexes revealed reversible uncomplicated oxidation whereas ferrocenyl–6-aminopenicillinic acid derivatives were found to exhibit adsorption waves in cathodic scans. Antibacterial activities of our ferrocenyl–antibiotic conjugates against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA) and Staphylococcus epidermidis bacterial strains were determined. Our experiments show significant antibacterial activity of ferrocenyl–6-aminopenicillinic acid bioconjugates against the bacterial strains tested. Contrary to that ferrocenyl–ampicillin derivatives were inactive. The inhibitory effects on the dd-carboxypeptidase 64-575 II exerted by our ferrocenyl–6-aminopenicillinic acid bioconjugates were established in the low nanomolar range. The tumor cell growth inhibition of representative ferrocenyl–ampicillin and ferrocenyl–6-aminopenicillinic acid bioconjugates against MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cell lines were studied in vitro. Similar to the antibacterial activity tests the assays in tumor cells revealed significant antiproliferative effects exerted by ferrocenyl–6-aminopenicillinic acid bioconjugates.