Interactions of Phenylalanine Derivatives with Human Tyrosinase: Lessons from Experimental and Theoretical tudies.

The pigmentation of the skin, modulated by different actors in melanogenesis, is mainly due to the melanins (protective pigments). In humans, these pigments' precursors are synthetized by an enzyme known as tyrosinase (TyH). The regulation of the enzyme activity by specific modulators (inhibitors or activators) can offer a means to fight hypo- and hyper-pigmentations responsible for medical, psychological and societal handicaps.

TrisOxine abiotic siderophores for technetium complexation: radiolabeling and biodistribution studies.

Background: Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit.

Exploiting HOPNO-dicopper center interaction to development of inhibitors for human tyrosinase.

In human, Tyrosinase enzyme (TyH) is involved in the key steps of protective pigments biosynthesis (in skin, eyes and hair). The use of molecules targeting its binuclear copper active site represents a relevant strategy to regulate TyH activities. In this work, we targeted 2-Hydroxypyridine-N-oxide analogs (HOPNO, an established chelating group for the tyrosinase dicopper active site) with the aim to combine effects induced by combination with a reference inhibitor (kojic acid) or natural substrate (tyrosine).

A highly active diradical cobalt(iii) catalyst for the cycloisomerization of alkynoic acids.

The first cobalt-catalysed cycloisomerisation of alkynoic acids is reported, thanks to the design of a well-defined diradical cobalt(iii) catalyst, in the absence of any additives. The high efficiency, regioselectivity and chemoselectivity are comparable to those of noble metal-based systems. The unique reactivity might be attributed to second coordination sphere effects.

Ni(II) Complexes of the Redox-Active Bis(2-aminophenyl)dipyrrin: Structural, Spectroscopic, and Theoretical Characterization of Three Members of an Electron Transfer Series.

The sterically hindered bis(2-aminophenyl)dipyrrin ligand HL was prepared. X-ray diffraction discloses a bifurcated hydrogen bonding network involving the dipyrrin and one aniline ring. The reaction of HL with one equivalent of nickel(II) in the air produces a paramagnetic neutral complex, which absorbs intensively in the Vis-NIR region.

Nickel(ii) radical complexes of thiosemicarbazone ligands appended by salicylidene, aminophenol and aminothiophenol moieties.

The nickel(ii) complexes of three unsymmetrical thiosemicarbazone-based ligands featuring a sterically hindered salicylidene (1), aminophenol (2) or thiophenol (3) moiety were synthesized and structurally characterized. The metal ion lies in an almost square planar geometry in all the complexes. The cyclic voltammetry (CV) curve of 1 shows an irreversible oxidation wave at E = 0.

Oxinobactin and sulfoxinobactin, abiotic siderophore analogues to enterobactin involving 8-hydroxyquinoline subunits: thermodynamic and structural studies.

The synthesis of two new iron chelators built on the tris-l-serine trilactone scaffold of enterobactin and bearing a 8-hydroxyquinoline (oxinobactin) or 8-hydroxyquinoline-5-sulfonate (sulfoxinobactin) unit has been described. The X-ray structure of the ferric oxinobactin has been determined, exhibiting a slightly distorted octahedral environment for Fe(III) and a Δ configuration. The Fe(III) chelating properties have been examined by potentiometric and spectrophotometric titrations in methanol-water 80/20% w/w solvent for oxinobactin and in water for sulfoxinobactin.

Iodination of verapamil for a stronger induction of death, through GSH efflux, of cancer cells overexpressing MRP1.

The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR) of cancer cells, was found to be modulated by verapamil, through stimulation of GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study, various iodinated derivatives of verapamil were synthesized, including iodination on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for the stimulation of GSH efflux by MRP1. The iodination, for nearly all compounds, led to a higher stimulation of GSH efflux.

Oxinobactin, a siderophore analogue to enterobactin involving 8-hydroxyquinoline subunits: synthesis and iron binding ability.

Oxinobactin, a siderophore analogue to enterobactin but possessing 8-hydroxyquinoline instead of catechol complexing subunits, has been synthesized starting from L-serine and 8-hydroxyquinoline. Comparative iron binding studies showed that oxinobactin is as effective as enterobactin for the complexation of Fe(III) at physiological pH but with improved complexing ability at acidic pH.

Radiolabeling of annexin A5 with (99m)Tc: comparison of HYNIC-Tc vs. iminothiolane-Tc-tricarbonyl conjugates.

In the perspective of expanding the use of annexin A5 (anx A5) as radioactive tracer of cell death in vivo, we recently described its radiolabeling with (99m)Tc-tricarbonyl [(99m)Tc(H(2)O)(3)(CO)(3)](+) via the mercaptobutyrimidyl group (anx A5-SH). The aim of the present article was to compare this new method with the HYNIC strategy (anx A5-HYNIC), recognized at present as the reference for the radiolabeling of proteins with (99m)Tc. Similar radiolabeling yields and better chemical stability were obtained with the [anx A5-SH-(99m)Tc-tricarbonyl] complex.

Vesicles to concentrate iron in low-iron media: an attempt to mimic marine siderophores.

Amphiphilic catechol-type iron chelators were studied with the aim of mimicking the properties of marine bacterial siderophores. The Fe(III) complexation constants and aqueous solution speciation of L(S10), a sulfonated catechol unit that has a C(10) lipophilic carbon chain connected by an amide linkage, were determined by spectrophotometric titration. The calculated value of pFe3+ is 18.

Design of iron chelators: syntheses and iron (III) complexing abilities of tripodal tris-bidentate ligands.

The interest in synthetic siderophore mimics includes therapeutic applications (iron chelation therapy), the design of more effective agents to deliver Fe to plants and the development of new chemical tools in order to study iron metabolism and iron assimilation processes in living systems. The design of ligands needs a rational approach for the understanding of the metal ion complexing abilities. The octahedral arrangement of donor atoms is the most favourable geometry, allowing the maximum possible distance between their formal or partial negative charges.

Verapamil and its derivative trigger apoptosis through glutathione extrusion by multidrug resistance protein MRP1.

This study demonstrates that verapamil and a newly synthesized verapamil derivative, NMeOHI(2), behave as apoptogens in multidrug resistance protein 1 (MRP1)-expressing cells. When treated with either verapamil or NMeOHI(2), surprisingly, baby hamster kidney-21 (BHK) cells transfected with human MRP1 were killed. Because parental BHK cells were not, as well as cells expressing an inactive (K1333L) MRP1 mutant, this indicated that cell death involved functional MRP1 transporter.

Early detection of chemoresistance in vivo through the use of a radiolabeled antisense oligonucleotide.

Aims: Radiolabeled antisense oligonucleotide to target the mRNA of the hmdr1 gene for diagnostic purposes is a new concept for evaluating the chemoresistance of tumors in vivo.

Methods And Results: An 18 mer complementary to the zone which contains the translation initiation codon of the hmdr1 gene was modified using one phosphoramidate group and one dimethoxytrityle group at the 5' and 3'ends. It permitted probe radiolabeling by 125I.