A five-coordinate copper complex with superoxide dismutase mimetic activity fromStreptomyces antibioticus

Schechinger, Thomas; Hiller, W.; Maichle, C.; Strählet, Joachim; Weser, Ulrich

doi:10.1007/bf01138069

Cited by 8 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,19 The formation constants of the 1:1 and 2:1 complexes of DFFTH 2 with several metal ions have been reported, 20 and the characterization of a 1:1 copper complex has been described. 21 We have earlier reported characterization of the 2:1 complexes of DFFTH 2 with Cr 3+ and Co 3+ . 22 While DFFTH 2 was found to be highly orally active, as a possible drug for iron decorporation it proved to be unacceptably toxic.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent¹

et al. 1996

View full text Add to dashboard Cite

Nordesferriferrithiocin, NDFFTH(2), is a derivative of the siderophore desferriferrithiocin, DFFTH(2), in which the methyl group is substituted by a hydrogen atom. Both compounds show high oral activity as possible drugs for the treatment of iron overload. While DFFTH(2) is significantly toxic, NDFFTH(2) exhibits a lower toxicity and offers a much better therapeutic window than other orally active iron chelators. In this study, complexes of DFFTH(2) and NDFFTH(2) with various trivalent metals have been synthesized and characterized. Five isomers (the maximum possible) have been observed in the case of [Co(DFFT)(2)](-) in solution, as proved by (1)H-NMR measurements. Although normally labile, complexes of Al(3+) ([Al(DFFT)(2)](-)) have been separated by HPLC. In general, DFFTH(2) forms kinetically inert complexes whereas complexes of NDFFTH(2) tend to isomerize quickly in solution, as indicated by CD spectroscopy of separated HPLC fractions of [Cr(NDFFT)(2)](-). The most stable isomers of the aluminum complexes of both ligands have been characterized by X-ray crystallography; K[Al(DFFT)(2)] crystallizes from methanol/diethyl ether in the orthorhombic space group P2(1)2(1)2 with a = 11.238(3) Å, b = 31.719(11) Å, c = 7.684(2) Å, V = 2739.2(24) Å(3), and Z = 4. This isomer has the mer-(N,O-Lambda)(S,S) configuration, while K[Al(NDFFT)(2)] crystallizes from methanol/diethyl ether in the space group P6(1) (a = 21.269(8) Å, c = 9.643(3) Å, V = 3777.8(42) Å(3), Z = 6) and has the same coordination geometry. The solution thermodynamics of the Al(3+), Ga(3+), and Fe(3+) complexes have been studied by spectrophotometric titration. The stability constants (log K) are 23.6(1), 29.2(3), and 31.04(3), respectively, for the DFFTH(2) complexes and 22.0(1), 27.8(2), and 29.09(3), respectively, for the NDFFTH(2) complexes. Cyclic voltammograms of both iron complexes have been recorded in water at a carbon disk working electrode and in DMF at a graphite working electrode. The reduction waves measured in DMF indicate no reversibility whereas in water a quasi-reversible reduction is observed. The reduction potentials (E(1/2)'s) in water are -166 mV for [Fe(DFFT)(2)](-) and -97 mV for [Fe(NDFFT)(2)](-) versus NHE. These potentials are well in the range for biological reductants, which makes possible an in vivo reduction mechanism for the iron removal from the siderophore.

show abstract

Section: Introductionmentioning

confidence: 98%

“…The formation constants of the 1:1 and 2:1 complexes of DFFTH 2 with several metal ions have been reported, and the characterization of a 1:1 copper complex has been described .…”

Section: Introductionmentioning

confidence: 99%

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent¹

et al. 1996

View full text Add to dashboard Cite

show abstract

Reactivity of active center analogs of Cu2Zn2 superoxide dismutase on activated polymorphonuclear leukocytes

Miesel

Hartmann

et al. 1990

Inflammation

View full text Add to dashboard Cite

In unseparated human blood the Cu2Zn2 superoxide dismutase mimetic reactivity of several differently coordinated low Mr copper chelates on TPA-activated polymorphonuclear leukocytes was evaluated and compared to their apo-chelates, CuSO4, and the native enzyme. Similar to intact superoxide dismutase, 350-400 nM Cu flexibly complexed in a di-Schiff base mode in CuPu(Py)2 and CuPu(Im)2, respectively, was sufficient to inhibit the oxidative burst-dependent superoxide production of human blood phagocytes by 50%. Acetate- or biuret-type copper chelates behaved like CuSO4. The catalytic superoxide dismuting reactivity of the di-Schiff base active center analogs of SOD was confirmed using isolated porcine PMNs. Even in the presence of 600 microM albumin as a model for competitive copper chelation in biological fluids CuPu(Py)2 and CuPu(Im)2 remained active. The stability during the Cu(I)/Cu(II) redox cycling was demonstrated in the presence of activated PMNs and albumin, taking advantage of the electron paramagnetic properties of CuPu(Py)2 and CuPu(Im)2.

show abstract

Inhibition of the G1-S transition of the cell cycle by inhibitors of deoxyhypusine hydroxylation

Hanauske-Abel

Park

Hanauske

et al. 1994

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

142

143

View full text Add to dashboard Cite

A five-coordinate copper complex with superoxide dismutase mimetic activity fromStreptomyces antibioticus

Cited by 8 publications

References 13 publications

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent¹

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent¹

Reactivity of active center analogs of Cu2Zn2 superoxide dismutase on activated polymorphonuclear leukocytes

Inhibition of the G1-S transition of the cell cycle by inhibitors of deoxyhypusine hydroxylation

Contact Info

Product

Resources

About

A five-coordinate copper complex with superoxide dismutase mimetic activity fromStreptomyces antibioticus

Cited by 8 publications

References 13 publications

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent1

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent1

Reactivity of active center analogs of Cu2Zn2 superoxide dismutase on activated polymorphonuclear leukocytes

Inhibition of the G1-S transition of the cell cycle by inhibitors of deoxyhypusine hydroxylation

Contact Info

Product

Resources

About

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent¹

Nordesferriferrithiocin. Comparative Coordination Chemistry of a Prospective Therapeutic Iron Chelating Agent¹