Coordination compounds in medicinal chemistry

Schwietert, Chad W.; McCue, John P.

doi:10.1016/s0010-8545(98)00205-7

Cited by 86 publications

(55 citation statements)

References 98 publications

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“…Currently used metal complexes (25)(26)(27)(28)(29)(30)(31) exhibit considerable toxicity. This has stimulated the interest in other compounds with more acceptable toxicity, such as ruthenium complexes (32)(33)(34)(35)(36).…”

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confidence: 99%

In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

Barna

Debache

Vock

et al. 2013

Antimicrob Agents Chemother

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bUpon the screening of 16 antiproliferative compounds against Toxoplasma gondii and Neospora caninum, two hydrolytically stable ruthenium complexes (compounds 16 and 18) exhibited 50% inhibitory concentrations of 18.7 and 41.1 nM (T. gondii) and 6.7 and 11.3 nM (N. caninum). To achieve parasiticidal activity with compound 16, long-term treatment (22 to 27 days at 80 to 160 nM) was required. Transmission electron microscopy demonstrated the rapid impact on and ultrastructural alterations in both parasites. These preliminary findings suggest that the potential of ruthenium-based compounds should thus be further exploited.T oxoplasma gondii and Neospora caninum are cyst-forming apicomplexan parasites that infect a wide range of hosts. In an immunocompetent host, infection with either parasite does not cause disease (1-3). N. caninum has emerged as one of the most important infectious causes of bovine abortion (4-6). In contrast, T. gondii causes toxoplasmosis in humans and many animal species, either in chronically infected individuals during a decrease in immunoreactivity or if a seronegative mother acquires a primary infection during pregnancy, leading to abortion or serious fetal abnormalities (7-9). Toxoplasmosis treatment is based on only a few chemotherapeutics with considerable adverse effects (10, 11). In Neospora-seropositive cattle, pregnancy and the associated immunomodulation are already sufficient to cause recrudescence, fetal damage, and abortion (2-6). Chemotherapy has been considered a promising option if effective drugs can be identified (12, 13). Several compounds were investigated in vitro (14-16), but only a few were evaluated in small-animal models (14,(17)(18)(19)(20)(21)(22)(23)(24).We have evaluated compounds originally synthesized as anticancer drugs. Currently used metal complexes (25-31) exhibit considerable toxicity. This has stimulated the interest in other compounds with more acceptable toxicity, such as ruthenium complexes (32-36). Effects of ruthenium compounds on some bacteria and parasites have been studied (37-46). "Classical ruthenium complexes" contain heteroatom ligands (e.g., azole derivatives), and NAMI-A and KP-1019 have been evaluated in phase I clinical trials for cancer treatment (47-49). Organometallic complexes are defined by at least one metal-carbon bond. The 6 -arene ruthenium(II) phosphite complexes 5, 6, 12, and 15 to 18 were characterized earlier (50), while [Ru( 6 -p-cymene)(bipyridine)Cl][Cl] 11 was synthesized as shown previously (51). Based on our experiences in the design of selective inhibitors of CYP11B2 (53) and CYP11B1 (54), the pyridine-based compounds 4, 7 to 10, and 14 were from a small in-house library of CYP enzyme inhibitors. 2,2=-Bipyridine 3 was obtained from Joachim W. Heinicke, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany. The cytotoxic lipophilic imidazolium salt 1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride 3 was synthesized as described previously (54-56). The arylimidamide DB745 2 (23) was kindly provided by David Bo...

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confidence: 99%

In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

Barna

Debache

Vock

et al. 2013

Antimicrob Agents Chemother

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“…In the past decade, there has been an upsurge of interest in the use of metallic compounds for both diagnosis and treatment of diseases [1,2]. Important in this regard is the ability of metal ions to bind proteins and peptides in vivo.F or the most particular interest, Cu(II) chelating agents have been observed to reduce inflammation associated with rheumatoid arthritis [3].…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of bis[aqua(2-hydroxy-5-chlorobenzylamino-N,Ndiacetato- κ4N,O,O',O'')copper(II)], [Cu(C11H10ClNO5)(H2O)]2

Gu¹

2012

Zeitschrift Für Kristallographie - New Crystal Structures

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“…Conversely it is possible to conclude that substances with a cytostatic effect inhibit the corresponding cyclic processes by transforming strong, marginally strong or critical cycles into weak ones. An example of this is the unspecific cytostatic effect of Ti(IV) complexes [11], which inhibit proteases, probably by attaching themselves to serine residues. 6 The rather complicated way of expressing this stems from the fact that the Boutwell model includes not only oncogenes such as benzo(a)pyrene but also promoters and further substances.…”

Section: Genesis Of Tumours: the Three-phase Modelmentioning

confidence: 99%

“…We now have a very good understanding of the roles of certain chemical elements (Ti, Fe, Cu, Pt) in the treatment of tumours [11], so the relevant biochemical processes and consequences can be investigated by formal methods such as those of stoichiometric network analysis.…”

Section: List Of the Metal-based Chemotherapeutic Agentsmentioning

confidence: 99%

“…59 bis-benzoylacetonato-bis-ethoxytitanium(IV)); inorganic Ti, into which this may be converted in vivo is extremely effective as a proteinase or peptidase inhibitor -a property which can be exploited therapeutically to combat bacteria, viruses (including HIV), and also tumours [11]. additional chemical signals from outside (even essential chemical elements such as iron can act as co-carcinogens).…”

Section: Classification Of Chemotherapeutic Agentsmentioning

confidence: 99%

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Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA): What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni²⁺, Cd²⁺) and to an Understanding of Chemotherapy?

Fränzle

Markert

2003

The Scientific World JOURNAL

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The biological application of stoichiometric network analysis (SNA) permits an understanding of tumour induction, carcinogenesis, and chemotherapy. Starting from the Biological System of the Elements, which provides a comprehensive treatment of the functions and distributions of chemical (trace) elements in biology, an attempt is made to interrelate the essential feature of biology andregrettably -of tumour genesis by superimposing SNA reasoning on common features of all crucial biological processes. For this purpose, aspects, effects, and drawbacks of autocatalysis (identical reproduction which can occur either under control or without control [in tumours]) are linked with the known facts about element distributions in living beings and about interference of metals with tumours (in terms of both chemotherapy and carcinogenesis). The essential role of autocatalysis in biology and the drawbacks of either controlled or spontaneous cell division can be used to understand crucial aspects of carcinogenesis and chemotherapy because SNA describes and predicts effects of autocatalysis, including phase effects that may be due to some kind of intervention. The SNAbased classifications of autocatalytic networks in cell biology are outlined here to identify new approaches to chemotherapy.

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Coordination compounds in medicinal chemistry

Cited by 86 publications

References 98 publications

In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

Crystal structure of bis[aqua(2-hydroxy-5-chlorobenzylamino-N,Ndiacetato- κ4N,O,O',O'')copper(II)], [Cu(C11H10ClNO5)(H2O)]2

Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA): What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni²⁺, Cd²⁺) and to an Understanding of Chemotherapy?

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Coordination compounds in medicinal chemistry

Cited by 86 publications

References 98 publications

In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

Crystal structure of bis[aqua(2-hydroxy-5-chlorobenzylamino-N,Ndiacetato- κ4N,O,O',O'')copper(II)], [Cu(C11H10ClNO5)(H2O)]2

Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA): What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni2+, Cd2+) and to an Understanding of Chemotherapy?

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Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA): What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni²⁺, Cd²⁺) and to an Understanding of Chemotherapy?