Ferrocenyl bioconjugates of ampicillin and 6-aminopenicillinic acid--synthesis, electrochemistry and biological activity.
We report on the synthesis of ferrocenyl-ampicillin and ferrocenyl-6-aminopenicillinic acid bioconjugates. Title compounds were characterized by (1)H 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.
Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland.
Joanna
J
Skiba
Aleksandra
A
Rajnisz
Kely Navakoski
KN
de Oliveira
Ingo
I
Ott
Jolanta
J
Solecka
Konrad
K
Kowalski
D000667:Ampicillin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004150:Dipeptidases / Q000037:antagonists & inhibitors; D055664:Electrochemical Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D000075163:Metallocenes; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D050296:Microbial Viability / Q000187:drug effects; D010084:Oxidation-Reduction; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D000075163:Metallocenes; D000667:Ampicillin; D010397:Penicillanic Acid; D004150:Dipeptidases; C019989:DD-carboxypeptidase-endopeptidase; C004408:aminopenicillanic acid; C004998:ferrocene