New developments for targeting drugs into central nervous system by means of a redox chemical delivery system

International audienc

New developments for targeting drugs into central nervous system by means of a redox chemical delivery system

International audienc

Synthesis of C 1- and C 3ν-symmetric porphyrin trimers based on triphenylmethane cores

This work describes the synthesis of a new class of tripodaphyrin derivatives with a triphenylmethane core. Both C₁- and C3ν-symmetric tetrahedral large molecules with covalently linked rigid elements were obtained

Synthesis of C1- and C3m-Symmetric Porphyrin Trimers Based on Triphenylmethane Cores

International audienceThis work describes the synthesis of a new class of tripodaphyrin derivatives with a triphenylmethane core. Both C1- and C3 -symmetric tetrahedral large molecules with covalently linked rigid elements were obtained

Exploring the synthesis and metal complexation behavior of mono and bis substituted hexaazamacrocyclic cage derivatives

A series of new hexaazamacrobicyclic cage ligands were synthesized and their metal complexation was investigated. Ligands synthesized included the benzyldiamsar, 4-bromobenzyldiamsar, 4-hydroxybenzyld iamsar, 4-methoxybenzyldiamsar, 4-(1-hydroxyethyl)benzyldiamsar, 4-nitrobenzyldiamsar bis-(benzyl)diamsar, bis-(4-bromobenzyl)dia msar, bis-(4-hydroxybenzyl)diamsar, bis-(4-methoxybenzyl)diamsar, bis-(4-(1-hydroxyethyl)benzyl)diamsar, bis-(4-nitrobenzyl)diamsar and bis-(4-aminobenzyl)diamsar. The complexation of the new ligands with Cu(II) and Co(II) at micromolar concentrations was performed at pH 3–9 and ambient temperature. All ligands complexed the Cu(II) rapidly within 5 min over the pH range 5–9. The complexation of Co(II) by the new ligands was significantly slower with optimum rate at pH 7–8 at ambient temperature. The substituents on the benzyl group of the new ligands was found to influence the formation of the Co(II) complexes, with the bis derivatives found to be comparatively slower. In contrast, the substitutents of mono- and bis-(4-substituted-benzyl)- hexaaza cages did not impact the rate of complexation of Cu(II). Overall the metal complexation was influenced by the desolvation energy of the metal ions as well as the substituents on the benzyl group. Nonetheless, the complexation study demonstrates that these new ligands could be Inorganic Chemistry Communications 82 (2017) 48–51 ⁎ Corresponding authors. E-mail addresses: [email protected] (E. Mume), [email protected],(C. Papamicaël). used both with Cu(II) and Co(II) at micromolar concentrations for further applications that require a physiological pH and ambient temperatur

Synthesis of sulfonic acid derivatives by oxidative deprotection of thiols using tert-butyl hypochlorite

International audienceStarting from alkyl halides or Michael acceptors, thioacetates were prepared in situ and further treated with t-BuOCl, affording the corresponding sulfonyl chlorides which were trapped with nucleophiles such as water, alcohol, or amines. The three steps can be achieved in a one-pot procedure. Oxidative deprotection also proved to be efficient with S-trityl and S-tert-butyl groups, making it a convenient route toward cysteic acid derivatives

The Influence of Amino Group Position on Aryl Moiety of SarAr on Metal Complexation and Protein Labelling

International audienceNew hexaazamacrobicyclic cage bi-functional chelators (BFCs), 1-N-(3-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (m-SarAr) and 1-N-(2-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (o-SarAr), were synthesised. Their complexation with selected transitions metal ions i.e. CuII, CoII, and CdII was investigated over a range of pH at micromolar concentrations. CuII was complexed by m-SarAr and o-SarAr rapidly within 5 min in pH range of 5–9 at ambient temperature. In contrast, the complexation of CoII and CdII by these ligands was slower. The conjugation efficiencies of p-SarAr, m-SarAr, and o-SarAr to bovine serum albumin (BSA) were compared under various reactions. Conditions were optimised to a molar ratio of BSA/N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC)/BFC of 1 : 250 : 50 in pH 5 buffer for 30 min at ambient temperature. Under these conditions, the average number of p-SarAr, m-SarAr, or o-SarAr attached to BSA were determined to be 2.21 ± 0.16, 4.90 × 10–1 ± 2.48 × 10–2, and 2.67 × 10–2 ± 2.67 × 10–3, respectively. This fundamental study clearly demonstrates that the position of the amine on the phenyl ring has a significant effect on the metal complexation and conjugation reactions with BSA

Synthesis of Technidazole: a potential new 99mTc ligand for imaging tumor hypoxia

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Design, Synthesis, and In Vitro Biological Activities of a Bio-Oxidizable Prodrug to Deliver Both ChEs and DYRK1A Inhibitors for AD Therapy

International audienceDespite their side effects, cholinesterase (ChE) inhibitors remain the only approved drugs to treat Alzheimer’s disease patients, along with the N-methyl-d-aspartate (NMDA) receptor antagonist memantine. In the last few years, the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has also been studied as a promising target for the development of new drugs for this pathology. In this context, and based on our previous characterization of bio-oxidizable prodrugs of potent acetylcholinesterase (AChE) inhibitors, we envisioned a strategy involving the synthesis of a bio-oxidizable prodrug of both ChE and DYRK1A inhibitors. To this end, we fixed our interest on a known potent inhibitor of DYRK1A, namely INDY. The designed prodrug of both ChE and DYRK1A inhibitors was successfully synthesized, connecting both inhibitors by a carbonate link. This prodrug and its corresponding drug were then evaluated as ChEs and DYRK1A inhibitors. Remarkably, in vitro results were in accordance with the starting hypothesis, showing a relative inactivity of the prodrug against DYRK1A and ChEs and a potent inhibition of ChEs by the oxidized form. Molecular docking and kinetic studies of ChE inhibition by the active compound are also discussed in this report