A New Heterobinuclear FeIIICuII Complex with a Single Terminal FeIII–O(phenolate) Bond. Relevance to Purple Acid Phosphatases and Nucleases

A novel heterobinuclear mixed valence complex [Fe^IIICu^II(BPBPMP)(OAc)_2]ClO_4, 1, with the unsymmetrical N_5O_2 donor ligand 2-bis[{(2-pyridylmethyl)aminomethyl}-6-{(2-hydroxybenzyl)(2-pyridylmethyl)} aminomethyl]-4-methylphenol (H_2BPBPMP) has been synthesized and characterized. A combination of data from mass spectrometry, potentiometric titrations, X-ray absorption and electron paramagnetic resonance spectroscopy, as well as kinetics measurements indicates that in ethanol/water solutions an [Fe^III-(nu)OH-Cu^IIOH_2]+ species is generated which is the likely catalyst for 2,4-bis(dinitrophenyl)phosphate and DNA hydrolysis. Insofar as the data are consistent with the presence of an Fe_III-bound hydroxide acting as a nucleophile during catalysis, 1 presents a suitable mimic for the hydrolytic enzyme purple acid phosphatase. Notably, 1 is significantly more reactive than its isostructural homologues with different metal composition (Fe^IIIM^II, where M^II is Zn^II, Mn^II, Ni^II,or Fe^II). Of particular interest is the observation that cleavage of double-stranded plasmid DNA occurs even at very low concentrations of 1 (2.5 nuM), under physiological conditions (optimum pH of 7.0), with a rate enhancement of 2.7 x 10^7 over the uncatalyzed reaction. Thus, 1 is one of the most effective model complexes to date, mimicking the function of nucleases

Guanosine prevents anhedonic-like behavior and impairment in hippocampal glutamate transport following amyloid-β_1–40 administration in mice.

Amyloid-beta (A beta) peptides are the major neuropathological hallmarks related with Alzheimer's disease (AD). A beta peptides trigger several biochemical mechanisms of neurotoxicity, including neuroinflammation and glutamatergic neurotransmission impairment. Guanosine is the endogenous guanine-derived nucleoside that modulates the glutamatergic system and the cellular redox status, thus acting as a neuroprotective agent. Here, we investigated the putative neuroprotective effect of guanosine in an AD-like mouse model. Adult mice received a single intracerebroventricular injection of A beta(1-40) (400 pmol/site) or vehicle and then were treated immediately, 3 h later, and once a day during the subsequent 14 days with guanosine (8 mg/kg, intraperitoneally). A beta(1-40) or guanosine did not alter mouse locomotor activity and anxiety-related behaviors. A beta(1-40)-treated mice displayed short-term memory deficit in the object location task that was prevented by guanosine. Guanosine prevented the A beta(1-40)-induced increase in latency to grooming in the splash test, an indicative of anhedonia. A beta(1-40) increased Na+-independent glutamate uptake in ex vivo hippocampal slices, and guanosine reversed it to control levels. The repeated administration of guanosine increased hippocampal GDP levels, which was not observed in the group treated with A beta plus guanosine. A beta(1-40) induced an increase in hippocampal ADP levels. A beta(1-40) decreased GFAP expression in the hippocampal CA1 region, an effect not modified by guanosine. No differences were observed concerning synaptophysin and NeuN immunolabeling. Together, these results show that guanosine prevents memory deficit and anhedonic-like behavior induced by A beta(1-40) that seem to be linked to glutamate transport unbalance and alterations on purine and metabolite levels in mouse hippocampus

Synthesis, electrochemical studies and anticancer activity of ferrocenyl oxindoles

A series of (E) and (Z)-ferrocenyl oxindoles were prepared by coupling substituted oxindoles to ferrocenylcarboxyaldehyde in the presence of morpholine as a catalyst. The redox behavior of these isomers was determined by cyclic voltammetry. The effects of the oxindole derivatives on the migration of human breast cancer cells were evaluated using the wound-healing assay and the Boyden chamber cell-migration assay. The most potent Z isomers 11b (IC50 = 0.89 μM), 12b (IC50 = 0.49 μM) and 17b (IC50 = 0.64 μM) could represent attractive new lead compounds for further development for cancer therapy39317338734

Synthesis, electrochemical studies and anticancer activity of ferrocenyl oxindoles

A series of (E) and (Z)-ferrocenyl oxindoles were prepared by coupling substituted oxindoles to ferrocenylcarboxyaldehyde in the presence of morpholine as a catalyst. The redox behavior of these isomers was determined by cyclic voltammetry. The effects of the oxindole derivatives on the migration of human breast cancer cells were evaluated using the wound-healing assay and the Boyden chamber cell-migration assay. The most potent Z isomers 11b (IC(50) = 0.89 mu M), 12b (IC(50) = 0.49 mu M) and 17b (IC(50) = 0.64 mu M) could represent attractive new lead compounds for further development for cancer therapy

New ionic targets of 3,3',5'-triiodothyronine at the plasma membrane of rat Sertoli cells

International audienceThe functions of Sertoli cells, which structurally and functionally support ongoing spermatogenesis, are effectively modulated by thyroid hormones, amongst other molecules. We investigated the mechanism of action of rT3 on calcium (45Ca2+) uptake in Sertoli cells by means of in vitro acute incubation. In addition, we performed electrophysiological recordings of potassium efflux in order to understand the cell repolarization, coupled to the calcium uptake triggered by rT3. Our results indicate that rT3 induces nongenomic responses, as a rapid activation of whole-cell potassium currents in response to rT3 occurred in <5 min in Sertoli cells. In addition, the rT3 metabolite, T2, also exerted a rapid effect on calcium uptake in immature rat testis and in Sertoli cells. rT3 also modulated calcium uptake, which occurred within seconds via the action of selective ionic channels and the Na+/K+ ATPase pump. The rapid response of rT3 is essentially triggered by calcium uptake and cell repolarization, which appear to mediate the secretory functions of Sertoli cells

Lawsone Dimerization in Cobalt(III) Complexes toward the Design of New Prototypes of Bioreductive Prodrugs

Dimerization of lawsone occurs upon reaction with Co­(BF₄)₂·6H₂O and <i>N</i>,<i>N</i>′-bis­(pyridin-2-ylmethyl)­ethylenediamine (py₂en) to produce the mononuclear complex [Co^III(bhnq)­(py₂en)]­BF₄·H₂O (<b>1</b>). This complex has been investigated as a prototype of a bioreductive prodrug, where the bhnq^2– ligand acts as a model for cytotoxic naphthoquinones. Cyclic voltammetry data in aqueous solution have shown a <i>quasi</i>-reversible Co^III/Co^II process at <i>E</i>_1/2 = −0.26 V vs Fc/Fc⁺. Reactivity studies revealed the dissociation of bhnq^2– from the complex upon reduction of <b>1</b> with ascorbic acid, and a dependence of the reaction rate on the oxygen concentration suggests the occurrence of redox cycling

Lawsone Dimerization in Cobalt(III) Complexes toward the Design of New Prototypes of Bioreductive Prodrugs

Dimerization of lawsone occurs upon reaction with Co­(BF₄)₂·6H₂O and <i>N</i>,<i>N</i>′-bis­(pyridin-2-ylmethyl)­ethylenediamine (py₂en) to produce the mononuclear complex [Co^III(bhnq)­(py₂en)]­BF₄·H₂O (<b>1</b>). This complex has been investigated as a prototype of a bioreductive prodrug, where the bhnq^2– ligand acts as a model for cytotoxic naphthoquinones. Cyclic voltammetry data in aqueous solution have shown a <i>quasi</i>-reversible Co^III/Co^II process at <i>E</i>_1/2 = −0.26 V vs Fc/Fc⁺. Reactivity studies revealed the dissociation of bhnq^2– from the complex upon reduction of <b>1</b> with ascorbic acid, and a dependence of the reaction rate on the oxygen concentration suggests the occurrence of redox cycling