Non-Platinum Chemotherapeutic Metallopharmaceuticals

Clarke, Michael J.; Zhu, Fuchun; Frasca, Dominic R.

doi:10.1021/cr9804238

Cited by 889 publications

(818 citation statements)

References 327 publications

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“…The reaction is always inhibited in the presence of tris, even when phosphate is in a two-fold excess, but proceeds with a strong linearization of DNA when tris is absent. We emphasize that these experiments do not show an activating effect of phosphate, but instead they show an inhibiting effect of tris 1 .…”

Section: Ph Buffer and Solvation Effectscontrasting

confidence: 45%

“…Peak areas for the Sc form were corrected using the factor 1.47 to account for its lower staining capacity by ethidium bromide [37] and used to calculate the percentage (%) of ACCEPTED MANUSCRIPT 7/28 each form (Sc, Nck and Lin). Standard deviation for repeatability (s r ) 1 for the peak area within the same gel was estimated as 0.8 % for the Sc form and 6 % for the Nck form. The s r of the whole experimental procedure, including the preparation of solutions and incubation was 10 %, 6 % and 3 %, for the Sc, Nck and Lin forms, respectively.…”

Section: Dna Cleavage Activitymentioning

confidence: 98%

“…In contrast the reducing agent MPA inhibits the nuclease activity, although some degradation of the Sc form into the Nck form still takes place. This inhibiting effect also takes place to 1 A Poisson distribution is used in the calculation of S, assuming the nicks are randomly distributed among the DNA population.…”

Section: Effect Of Light Air and Activating Agentsmentioning

confidence: 99%

“…The presence of complex seems to concentrate the DNA molecules in phosphate buffer ( Fig. 7-A), while in hepes buffer it makes them more 1 Being an excellent chelating agent, EDTA will surely affect the speciation of vanadium in solution, removing the coordinated acac ligands to a considerable extent. However, although the stability constant for V IV O(EDTA) (logβ=18.…”

Section: Atomic Force Microscopymentioning

confidence: 99%

“…These compounds are relevant for two main reasons: (a) as possible therapeutic agents in cancer chemotherapy, which is the case of gallium, ruthenium, rhodium, titanium, tin and vanadium compounds [1]; (b) as potential substitutes for natural nuclease enzymes on gene manipulation techniques, for which inorganic nucleases showing site specificity are particularly relevant [2,3].…”

Section: Introductionmentioning

confidence: 99%

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DNA cleavage activity of VIVO(acac)2 and derivatives

Butenko

Tomaz

Nouri

et al. 2009

Journal of Inorganic Biochemistry

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Section: Ph Buffer and Solvation Effectscontrasting

confidence: 45%

Section: Dna Cleavage Activitymentioning

confidence: 98%

Section: Effect Of Light Air and Activating Agentsmentioning

confidence: 99%

Section: Atomic Force Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA cleavage activity of VIVO(acac)2 and derivatives

Butenko

Tomaz

Nouri

et al. 2009

Journal of Inorganic Biochemistry

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Metal‐Based Drugs

Shaw

2005

Encyclopedia of Inorganic Chemistry

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Metallopharmaceuticals have a long history in the development of chemotherapy. The more recent success of cisplatin and six related Pt‐based antitumor drugs, and longer histories of chrysotherapy (gold treatments) for arthritis, bismuth antiulcer agents, and silver‐, antimony‐ and arsenic‐based antimicrobial agents demonstrate that the periodic table represents a potential wealth of medicinal agents to be explored and developed in the future. This article reviews the use of twelve elements (Ag, As, Au, Bi, Ga, Li, Pt, Ru, Sb, Sn, Ti, V) for a wide variety of diseases and disorders. The current state of research on particular applications varies widely – from promising treatments that have not yet reached the clinic to those that are well established empirically despite uncertain mechanisms of action. The array of antitumor agents licensed or in clinical trials includes compounds of As, Ga, Ru, and Ti, in addition to platinum. There are also exciting efforts to apply known treatments or biological properties to new diseases by taking advantage of extensive databases, for example, developing antitumor agents from organotin complexes that have long been used as fungicides and antifouling agents, and antimicrobial agents from gold complexes. The ability to modulate the properties of metal complexes by choice of the oxidation state (Au I vs Au III ; Pt II vs Pt IV ; V III , V IV & V V , etc.) and design of the medical carrier ligands (e.g. 1,2‐diaminocyclohexane vs two ammine ligands for Pt antitumor agents) allows targeting of particular tissues or cells and balancing of lipophilicity, solubility, and reactivity to balance therapeutic activity against toxicity. Many, if not most, metallopharmaceuticals are prodrugs that undergo redox changes and/or ligand exchange reactions in vivo to generate the active species. Hence, research on metallodrug metabolism and pharmacology is as important as the initial medicinal screening of the agents.

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