Metal Compounds as Enzyme Inhibitors

Gasser, Gilles; Metzler‐Nolte, Nils

doi:10.1002/9783527633104.ch12

Cited by 27 publications

(17 citation statements)

References 187 publications

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“…9–12 Metal complexes have been used as drugs in a variety of diseases, as exemplified by the continued success of the platinum complex, cis-PtCl 2 (NH 3 ) 2 (cisplatin), as an anticancer drug. 13–15 This important breakthrough has indeed stimulated a renewed interest in metal complex based chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

Hubin

Amoyaw

Roewe

et al. 2014

Bioorganic & Medicinal Chemistry

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Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn2+ complex of this ligand was the most potent with IC50s of 0.127 and 0.157 µM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better antimalarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn2+. Few of the Cu2+ and Fe2+ complexes also showed improvement in activity but Ni2+, Co2+ and Zn2+ complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development.

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Section: Introductionmentioning

confidence: 99%

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

Hubin

Amoyaw

Roewe

et al. 2014

Bioorganic & Medicinal Chemistry

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“…[1][2][3][4][5][6] In all cases, successful approaches must be appropriate for intracellular environments with little availability of free transition metals due to transport and sequestration processes. One approach uses exchange-inert, coordinatively-saturated metal centers to serve as a framework for the construction of new molecular shape, an idea that has recently led to many useful inhibitors of kinases and other enzyme targets (Fig.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting prolyl isomerase activity by hybrid organic–inorganic molecules containing rhodium(II) fragments

Coughlin

Kundu

Cooper

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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“…[6][7][8] In addition, it is known that a certain concentration of metal ions leads to the denaturation of protein. [9,10] For example, Chen et al [11] showed that several metal ions induced the aggregation of amyloid β-protein.…”

Section: Introductionmentioning

confidence: 99%

Protein cohesion induced by metal ions observed with fluorescence correlation spectroscopy

Inoue

Aoki

Fujiwara

2013

Journal of Environmental Science and Health, Part A

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Nine metal ions were evaluated in the point of denaturating action of proteins. When some metal ions were added to the diluted protein solutions, aggregates appear: stronger denaturation causes the appearance of the larger-size aggregate. The size of the aggregatates are determined by fluorescence correlation spectroscopy (FCS). Green fluorescent protein (ZsGreen) and PE(phycoerythrin)-conjugated human-antibody monoclonal protein were employed as the target protein, of which solution was diluted 100-500 times and mixed with metal ions. According to this process, the denaturation power of metal ions is in the order of Mn(2+)≈ Fe(2+)< Co(2+)< Ni(2+)< Tl(+)< Cd(2+)< Cu(+)< Cu(2+)< Pb(2+)for ZsGreen, and Tl(+)≈ Ni(2+)< Cd(2+)< Fe(2+)< Cr(3+)≪ Pb(2+)for PE-conjugated antibody protein. Pb(2+)exhibits the strongest power of denaturation. In the case of ZsGreen, the denaturation power of metal ions is on the order of the Irving-Williams series, which provide the coordination tendency against ligands possessing nitrogen and oxygen. The present method with FCS is effective to evaluate the denaturation power of metal ions against proteins.

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Metal Compounds as Enzyme Inhibitors

Cited by 27 publications

References 187 publications

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

Inhibiting prolyl isomerase activity by hybrid organic–inorganic molecules containing rhodium(II) fragments

Protein cohesion induced by metal ions observed with fluorescence correlation spectroscopy

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