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

Skiba, Joanna; Rajnisz, Aleksandra; Oliveira, Kely Navakoski de; Ott, Ingo; Solecka, Jolanta; Kowalski, Konrad

doi:10.1016/j.ejmech.2012.09.023

Cited by 35 publications

(24 citation statements)

References 35 publications

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“…The desired metallocenyl-β-lactams have been obtained by an active ester methodology. 26 Compounds were characterized by 1 H NMR, 13 C NMR, FTIR, MS and elemental analysis, confirming the proposed structures. 1 H-NMR spectra of 2–7 are shown in the SI.…”

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confidence: 57%

Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase

et al. 2017

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A series of six novel metallocenyl-7-ADCA (metallocenyl = ferrocenyl or ruthenocenyl; 7-ADCA = 7-aminodesacetoxycephalosporanic acid) conjugates were synthesized and their antibacterial properties evaluated by biochemical and microbiological assays. The ruthenocene derivatives showed a higher level of inhibition of DD-carboxypeptidase 64-575, a Penicillin Binding Protein (PBP), than the ferrocene derivatives and the reference compound penicillin G. Protein X-ray crystallographic analysis revealed a covalent acyl-enzyme complex of a ruthenocenyl compound with CTX-M β-lactamase E166A mutant, corresponding to a similar complex with PBPs responsible for the bactericidal activities of these compounds. Most interestingly, an intact compound was captured at the crystal-packing interface, elucidating for the first time the structure of a metallocenyl β-lactam compound that previously eluded small molecule crystallography. We propose that protein crystals, even from biologically unrelated molecules, can be utilized to determine structures of small molecules.

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confidence: 57%

Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase

et al. 2017

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“…The modification of the biological effects of some biologically active molecules by ferrocene is an active field of study and many other complexes were synthesized and studied for their biological activity including ferrocenylphenols (Hillard et al, 2007;Hamels et al, 2009), ferrocenyl-ampicillin and ferrocenyl-6-aminopenicillinic acid (Skiba et al, 2012) or ferrocenyl-flavonoids (Monserrat et al, 2013). Also, our preliminary results with ferrocenylchalcones confirmed antiproliferative potential of these compounds.…”

Section: Iron Complexes As Potential Anti-cancer Compoundssupporting

confidence: 61%

Organometallic iron complexes as potential cancer therapeutics.

2014

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Metal-containing drugs have long been used for medicinal purposes in more or less empirical way. The potential of these anticancer agents has only been fully realised and explored since the discovery of the biological activity of cisplatin. Cisplatin and carboplatin have been two of the most successful anti-cancer agents ever developed, and are currently used to treat ovarian, lung and testicular cancers. They share certain side effects, so their clinical use is severely limited by dose-limiting toxicity. Inherent or acquired resistance is a second problem often associated with platinum-based drugs, with further limits of their clinical use. These problems have prompted chemists to employ different strategies in development of the new metal-based anticancer agents with different mechanisms of action. There are various metal complexes still under development and investigation for the future cancer treatment use. In the search for novel bio-organometallic molecules, iron containing anti-tumoral agents are enjoying an increasing interest and appear very promising as the potential drug candidates. Iron, as an essential cofactor in a number of enzymes and physiological processes, may be less toxic than non essential metals, such as platinum. Up to now, some of iron complexes have been tested as cytotoxic agents and found to be endowed with an antitumor activity in several in vitro tests (on cultured cancer cell lines) and few in vivo experiments (e. g. on Ehrlich's ascites carcinoma). Although the precise molecular mechanism is yet to be defined, a number of observations suggest that the reactive oxygen species can play important role in iron-induced cytotoxicty. This review covers some relevant examples of research on the novel iron complexes.

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“…While 1 was unable to reach the level of inhibition seen with ampicillin against the MRSA strain, the addition of the ruthenocenyl moiety to 6-APA showed much higher levels of inhibition than 6-APA alone (Table S1). The addition of the ruthenocene moiety also showed greater inhibition than the 6-APA ferrocene conjugate that we previously studied, 24 indicating that the larger ruthenium ion may confer more potent antibacterial properties than the smaller iron ion. Compound 1 was tested in vitro for hemolytic activity, and no activity was observed on human erythrocytes, which is one of the conditions for safe antibiotic use.…”

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Antibacterial properties and atomic resolution X-ray complex crystal structure of a ruthenocene conjugated β-lactam antibiotic

et al. 2015

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

Cited by 35 publications

References 35 publications

Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase

Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase

Organometallic iron complexes as potential cancer therapeutics.

Antibacterial properties and atomic resolution X-ray complex crystal structure of a ruthenocene conjugated β-lactam antibiotic

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