Ferrocene–Biotin Conjugates: Synthesis, Structure, Cytotoxic Activity and Interaction with Avidin

Błauż, Andrzej; Rychlik, Błażej; Makal, Anna; Szulc, Katarzyna; Strzelczyk, P.; Bujacz, G.; Zakrzewski, Janusz; Woźniak, Krzysztof; Plażuk, Damian

doi:10.1002/cplu.201600320

Cited by 10 publications

(2 citation statements)

References 71 publications

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“…The presence of the dual loop conformations decreases the binding site rigidity and consequently increases the chances for TEP to be located in different conformations. This was already detected for PDB 5HLM, 50 PDB 3FDC 51 and particularly for PDB 4JHQ. 52 The TEP planarity is unambiguously determined into the binding pocket by the unbiased difference Fo-Fc map (Figure 1B).…”

Section: Crystal Structure Of Avidin-tep Complexmentioning

confidence: 63%

The avidin‐theophylline complex: A structural and computational study

2023

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The interaction between avidin and its counterpart biotin is one of central importance in biology and has been reproposed and studied at length. However, the binding pocket of avidin is prone to promiscuous binding, able to accommodate even non‐biotinylated ligands. Comprehending the factors that distinguish the extremely strong interaction with biotin to other ligands is an important step to fully picture the thermodynamics of these low‐affinity complexes. Here, we present the complex between chicken white egg avidin and theophylline (TEP), the xanthine derivative used in the therapy of asthma. In the crystal structure, TEP lies in the biotin‐binding pocket with the same orientation and planarity of the aromatic ring of 8‐oxodeoxyguanosine. Indeed, its affinity for avidin measured by isothermal titration calorimetry is in the same μM range as those obtained for the previously characterized nucleoside derivatives. By the use of molecular dynamic simulations, we have investigated the most important intermolecular interactions occurring in the avidin‐TEP binding pocket and compared them with those obtained for the avidin 8‐oxodeoxyguanosine and avidin‐biotin complexes. These results testify the capability of avidin to complex purely aromatic molecules.

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Section: Crystal Structure Of Avidin-tep Complexmentioning

confidence: 63%

The avidin‐theophylline complex: A structural and computational study

2023

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“…Such a strategy turned out to be fruitful in the case of modification of many natural products (for a review, see e.g., ref 20) and�except for a single study 21 �was not employed for folates so far. We demonstrated previously that inserting an organometallic component in a biologically active molecule may dramatically alter its properties, e.g., turn a vitamin into a toxin 22 or change the molecular target of the parental compound. 23 Therefore, we investigated if the introduction of a ferrocenyl moiety affected the biological properties of MTX (Figure 1, compounds 1−3).…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Biological Properties of Ferrocenyl and Organic Methotrexate Derivatives

Rózga,

Błauż,

Moscoh Ayine-Tora

et al. 2024

ACS Omega

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Synthesis and biological activity of two series of modified side chain methotrexate (MTX) derivatives are presented, one with a ferrocenyl moiety inserted between the pteroyl and glutamate portions of the molecule and the other with glutamate substituted for short chain amino acids. Ferrocenyl derivatives of MTX turned out to be rather moderate inhibitors of dihydrofolate reductase (DHFR) although molecular modeling suggested more effective interactions between these compounds and the target enzyme. More interestingly, ferrocene-decorated MTX derivatives were able to impede the proliferation of four murine and human cell lines as well as their methotrexate-resistant counterparts, overcoming the multidrug resistance (MDR) barrier. They were also able to directly interact with Abcc1, an MDR protein. Of the amino acid pteroyl conjugates, the γ-aminobutyric acid derivative was an efficient inhibitor of DHFR but had no effect on cell proliferation in the concentration range studied while a taurine conjugate was a poor DHFR inhibitor but able to affect cell viability. We postulate that modification of the methotrexate side chain may be an efficient strategy to overcome efflux-dependent methotrexate resistance.

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Synthesis and in vitro Biological Evaluation of Ferrocenyl Side‐Chain‐Functionalized Paclitaxel Derivatives

et al. 2017

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Taxanes, including paclitaxel, are widely used in cancer therapy. In an attempt to overcome some of the disadvantages entailed with taxane chemotherapy, we devised the synthesis of ferrocenyl-functionalized paclitaxel derivatives and studied their biological properties. The cytotoxic activity was measured with a panel of human cancer cell lines of various tissue origin, including multidrug-resistant lines. A structure-activity study of paclitaxel ferrocenylation revealed the N-benzoyl-ferrocenyl-substituted derivative to be the most cytotoxic. In contrast, substitution of the 3'-phenyl group of paclitaxel with a ferrocenyl moiety led to less potent antiproliferative compounds. However, these agents were able to overcome multidrug resistance, as they were virtually unrecognized by ABCB1, a major cellular exporter of taxanes. Interestingly, the redox properties of these ferrocenyl derivatives appear to play a less important role in their mode of action, as there was no correlation between intracellular redox activity and cytotoxicity/cell-cycle distribution. The antiproliferative activity of ferrocenyl taxanes strongly depends on the substitution position, and good tubulin polymerization inducers, as confirmed by molecular docking, were usually more cytotoxic, whereas compounds with stronger pro-oxidative properties exhibited lower antiproliferative activity.

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Ferrocene–Biotin Conjugates: Synthesis, Structure, Cytotoxic Activity and Interaction with Avidin

Cited by 10 publications

References 71 publications

The avidin‐theophylline complex: A structural and computational study

The avidin‐theophylline complex: A structural and computational study

Synthesis and Biological Properties of Ferrocenyl and Organic Methotrexate Derivatives

Synthesis and in vitro Biological Evaluation of Ferrocenyl Side‐Chain‐Functionalized Paclitaxel Derivatives

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