Trinuclear Schiff base complexes with uranium(V) and copper(II) or zinc(II) ions

Treatment of the uranium(IV) complexes [{ML¹(py)}₂U^IV] (M = Cu, Zn; L¹ = N,N′-bis(3-hydroxysalicylidene)-1,3-propanediamine) with silver nitrate in pyridine led to the formation of the corresponding cationic uranium(V) species which were found to be thermally unstable and were converted back into the parent U^IV complexes; no electron transfer was observed in solution between the U^IV and U^V compounds. In the crystals of [{ML¹(py)}₂U^IV][{ML¹(py)}₂U^V][NO₃], the neutral U^IV and cationic U^V species are clearly identified by the distinct U–O distances. Similar reaction of [{ZnL²(py)}₂U^IV] [L² = N,N′-bis(3-hydroxysalicylidene)-1,4-butanediamine] with AgNO₃ gave crystals of [{ZnL²(py)}U^V{ZnL²(py)₂}][NO₃] but the copper counterpart was not isolated. Crystals of [{ZnL¹(py)}₂U^V][OTf] · THF (OTf = OSO₂CF₃) were obtained fortuitously from the reaction of [Zn(H₂L¹)] and U(OTf)₃.     

La Τ-régularité des mesures Gaussiennes

Summary We give a simple proof of the fact that a Radon gaussian measure on a locally convex vector space is carried by a countable union of metrisable compact sets. We show that a separable centered gaussian process with continuous covariance which is defined on a Polish space X, and is a.e. unbounded on any open set, has a.e. dense trajectories in X × . These results allow us to show that for any set I, any gaussian measure on ^I is -smooth.     

Mechanism of Formation of Peroxocarbonates RhOOC(O)O(Cl)(P)(3) and Their Reactivity as Oxygen Transfer Agents Mimicking Monooxygenases. The First Evidence of CO(2) Insertion into the O-O Bond of Rh(eta(2)-O(2)) Complexes

Extended labeling experiments have shown that formation of rhodium peroxocarbonate from CO(2) and [RhCl(eta(2)-O(2))(P)(3)] (P is PEt(2)Ph or PEtPh(2)) proceeds through O-O bond cleavage and CO(2) insertion. O-transfer to ancillary phosphine ligand to give R(3)P=O selectively (>85%) involves the Rh-linked O atom of the peroxo group of RhCl(CO(4))(P)(3).     

Barycentres de sous-mesures pathologiques

Resumé On construit un groupe compact et une sous-mesure pathologique sur ce groupe dont la convolée avec la mesure de Haar n'est pas pathologique.     

Phytochemical Analysis and Understanding the Antioxidant and Anticancer Properties of Methanol Extract from Litsea glutinosa: In Vitro and In Vivo Studies

Litsea glutinosa (L. glutinosa) is considered an evidence-based medicinal plant for the treatment of cancer, the leading cause of death worldwide. In our study, the in vitro antioxidant and in vivo anticancer properties of an essential ethno-medicinal plant, L. glutinosa, were examined using non-toxic doses and a phytochemical analysis was executed using gas-chromatography–mass-spectrometry. The in vitro antioxidant study of the L. glutinosa methanolic extract (LGBME) revealed a concentration-dependent antioxidant property. The bark extract showed promising antioxidant effects in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. The strongest antioxidant activity was demonstrated at the maximum concentration (50 µg/mL). The IC₅₀ values of the LGBME and BHT were 5.51 and 5.01 µg/mL, respectively. At the same concentration, the total antioxidant capacity of the LGBME was 0.161 µg/mL and the ferric reducing antioxidant power assay result of the LGBME was 1.783 µg/mL. In the cytotoxicity study, the LD₅₀ of the LGBME and gallic acid were 24.93 µg/mL and 7.23 µg/mL, respectively. In the in vivo anticancer-activity studies, the LGBME, particularly at a dose of 150 mg/kg/bw, showed significant cell-growth inhibition, decreased tumor weight, increased mean survival rate, and upregulated the reduced hematological parameters in EAC (Ehrlich’s ascites carcinoma)-induced Swiss albino mice. The highest cell-growth inhibition, 85.76%, was observed with the dose of 150 mg/kg/bw. Furthermore, the upregulation of pro-apoptotic genes (p53, Bax) and the downregulation of anti-apoptotic Bcl-2 were observed. In conclusion, LGBME extract has several bioactive phytoconstituents, which confirms the antioxidant and anticancer properties of L. glutinosa.     

Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides

Due to the urgent need of innovation in the antimalarial therapeutic arsenal, a series of thirty-seven ring-substituted N-arylcinnamanilides prepared by microwave-assisted synthesis were subjected to primary screening against the chloroquine-sensitive strain of P. falciparum 3D7/MRA-102. The lipophilicity of all compounds was experimentally determined as the logarithm of the capacity factor k, and these data were subsequently used in the discussion of structure-activity relationships. Among the screened compounds, fourteen derivatives exhibited IC₅₀ from 0.58 to 31 µM, whereas (2E)-N-(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide (24) was the most effective agent (IC₅₀ = 0.58 µM). In addition, (2E)-N-[2,6-dibromo-4-(trifluoromethyl)- phenyl]-3-phenylprop-2-enamide (36), (2E)-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-phenylprop- 2-enamide (18), (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide (23), and (2E)-3-phenyl-N-(3,4,5-trichlorophenyl)prop-2-enamide (33) demonstrated efficacy in the IC₅₀ range from 2.0 to 4.3 µM, comparable to the clinically used standard chloroquine. The results of a cell viability screening performed using THP1-Blue™ NF-κB cells showed that none of these highly active compounds displayed any significant cytotoxic effect up to 20 μM, which makes them promising Plasmodium selective substances for further investigations.     

Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na+ Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases

Voltage-gated Na⁺ (Na_V) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na_V channel ligands. With the objective of discovering new blockers of Na_V channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of Na_V channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC₅₀. These five alkaloids were then assayed using the Na⁺ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNa_V1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na⁺ currents elicited by the hNa_V1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na⁺ currents elicited by the hNav1.2 and hNav1.6 channels, with IC₅₀ values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block Na_V channels, with promising therapeutical applications.     

A Water Molecule Triggers Guest Exchange at a Mono-Zinc Centre Confined in a Biomimetic Calixarene Pocket: a Model for Understanding Ligand Stability in Zn Proteins

In this study, the ligand exchange mechanism at a biomimetic Zn^II centre, embedded in a pocket mimicking the possible constrains induced by a proteic structure, is explored. The residence time of different guest ligands (dimethylformamide, acetonitrile and ethanol) inside the cavity of a calix[6]arene-based tris(imidazole) tetrahedral zinc complex was probed using 1D EXchange SpectroscopY NMR experiments. A strong dependence of residence time on water content was observed with no exchange occurring under anhydrous conditions, even in the presence of a large excess of guest ligand. These results advocate for an associative exchange mechanism involving the transient exo-coordination of a water molecule, giving rise to 5-coordinate Zn^II intermediates, and inversion of the pyramid at the Zn^II centre. Theoretical modelling by DFT confirmed that the associative mechanism is at stake. These results are particularly relevant in the context of the understanding of kinetic stability/lability in Zn proteins and highlight the key role that a single water molecule can play in catalysing ligand exchange and controlling the lability of Zn^II in proteins.     

Synthesis of Carbapenems Containing Peptidoglycan Mimetics and Inhibition of the Cross-Linking Activity of a Transpeptidase of l,d Specificity

The carbapenem class of β-lactams has been optimized against Gram-negative bacteria producing extended-spectrum β-lactamases by introducing substituents at position C2. Carbapenems are currently investigated for the treatment of tuberculosis as these drugs are potent covalent inhibitors of l,d -transpeptidases involved in mycobacterial cell wall assembly. The optimization of carbapenems for inactivation of these unusual targets is sought herein by exploiting the nucleophilicity of the C8 hydroxyl group to introduce chemical diversity. As β-lactams are structure analogs of peptidoglycan precursors, the substituents were chosen to increase similarity between the drug and the substrate. Fourteen peptido-carbapenems were efficiently synthesized. They were more effective than the reference drug, meropenem, owing to the positive impact of a phenethylthio substituent introduced at position C2 but the peptidomimetics added at position C8 did not further improve the activity. Thus, position C8 can be modified to modulate the pharmacokinetic properties of highly efficient carbapenems.