Reprint of "Inspired by flowers: synthetic routes to scalemic deltamethrinic acid" [Bioorg. Med. Chem. 17 (2009) 2555-2575].

This review reports different syntheses of deltamethrinic acid, especially those originating from our laboratory. Deltamethrinic acid is a synthetic compound whose structure is inspired from those present in the flower head of the plant Chrysanthemum cinerariifolium. Its ester 'deltamethrin' exhibits an extremely high insecticidal activity (DDTx35.

Inspired by flowers: synthetic routes to scalemic deltamethrinic acid.

This review reports different syntheses of deltamethrinic acid, especially those originating from our laboratory. Deltamethrinic acid is a synthetic compound whose structure is inspired from those present in the flower head of the plant Chrysanthemum cinerariifolium. Its ester 'deltamethrin' exhibits an extremely high insecticidal activity (DDTx35.

Diastereoselective bromination of compounds bearing a cyclohex-3-enol moiety: application to the enantioselective synthesis of (1R)-cis-deltamethrinic acid.

(1R)-cis-chrysanthemic acid has been prepared in a few steps with complete control of the relative and absolute stereochemistry. Some mechanistic aspect of the addition of bromine to the C,C double bond of 2,2,5,5-tetramethylcyclohex-3-enol is disclosed.

Selected regiocontrolled transformations applied to the synthesis of (1S)-cis-chrysanthemic acid from (1S)-3,4-epoxy-2,2,5,5-tetramethylcyclohexanol.

(1S)-cis-Chrysanthemic acid has been prepared in a few steps with complete control of the relative and absolute stereochemistry using regiocontrolled epoxide ring opening, diol mono-oxidation and cyclopropanation.

Up-regulation of cathepsin B expression and enhanced secretion in mitochondrial DNA-depleted osteosarcoma cells.

Background Information: mtDNA (mitochondrial DNA) mutations that impair oxidative phosphorylation can contribute to carcinogenesis through the increased production of reactive oxygen species and through the release of proteins involved in cell motility and invasion. On the other hand, many human cancers are associated with both the up-regulation and the increased secretion of several proteases and heparanase. In the present study, we tried to determine whether the depletion in mtDNA could modulate the expression and/or the secretion of some lysosomal hydrolases in the 143B osteosarcoma cells, as these mtDNA-depleted cells are characterized by a higher degree of invasiveness than the parental cells.

Ultrastructural features of hepatocytes in cultured Eurasian perch ( Perca fluviatilis L.) as affected by nutritional and husbandry conditions.

A wide range of factors can be attributed to the syndrome of fatty liver observed in some cultured fish species. The objective of the study was therefore to quantify different hepatocyte ultrastructural features as potentially influenced by twelve nutritional and husbandry factors, in order to discriminate the most influent factors in Eurasian perch (Perca fluviatilis), a typical carnivorous temperate fish species. Twenty-four groups of juveniles (initial weight 57.

Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core.

The synthesis and enzyme inhibitor properties of reversible type B monoamine oxidase inhibitors are described. These compounds belong to the 5H-indeno[1,2-c]pyridazine family and possess a hydrophobic benzyloxy or 4,4,4-trifluorobutoxy side chain which, in contrast to a previous assignment, has been unambiguously located at C(8) of the heterocyclic moiety. Investigation of the regioisomeric structures establishes that substitution of the 5H-indeno[1,2-c]pyridazin-5-one core at C(7) vs C(8) dramatically influences the MAO-inhibiting properties of these compounds.

Multiscale approach of fish responses to different types of environmental contaminations: a case study.

In order to study the responses of wild fish to environmental contaminations, different sites (two references and three contaminated) were sampled across the Walloon hydrographical network (southern Belgium). The status of fish communities was characterized according to an index of biotic integrity (IBI). Furthermore, population structure, reproductive parameters and biochemical assays were performed on chub (Leuciscus cephalus) as sentinel species.

(2RS,5SR,6SR)-methyl 4-{cis-2-[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxymethyl]-6-hydroxy-3-phenylmorpholino}benzenesulfinate.

The title compound, C30H34FNO7S, is a key intermediate in the design of dual 5-LOX (5-lipoxygenase)/COX-2 (cyclooxygenase-2) inhibitors. The compound crystallizes as a racemate. Linear hydrogen-bonded chains are aligned along the [201] direction, and stacked pi-pi interactions and C-H.

A new potential cyclooxygenase-2 inhibitor, pyridinic analogue of nimesulide.

In this paper, the binding mode of original pyridinic compounds structurally related to nimesulide, a preferential cyclooxygenase (COX)-2 inhibitor, is analyzed by docking simulations in order to understand structure-activity relationships of this family. Structural modifications are proposed to reverse the selectivity of the more active inhibitor of the series characterized by a preferential activity on COX-1. On the basis of these modifications, a new compound with a bromo substituent was designed and showed a COX-2 selective inhibition.

Endolysosomal transport of newly-synthesized cathepsin D in a sucrose model of lysosomal storage.

Newly-synthesized soluble lysosomal enzymes are transported from the trans-Golgi network to lysosomes by a mannose 6-phosphate receptor-mediated pathway. Lysosomal storage of indigestible material has been reported to perturb the biosynthesis and the fate of lysosomal hydrolases. In this study, we have focused our attention on the last steps in the transport of newly-synthesized cathepsin D to lysosomes in sucrose-treated WI-38 fibroblasts.

Synthesis of primary-alkyl selenols and selenides from primary-alkyl thiols involving diphenyl sulfonium salts.

Hexyl thiol has been transformed to hexyl selenol and related selenides and selenocyanate by substitution of the corresponding hexyldiphenylsulfonium tetrafluoroborate with selenium nucleophiles.

1-[4-(Methylsulfonyl)phenyl]-5-phenyl-1H-pyrazole derivatives.

Three related compounds containing a pyrazole moiety with vicinal phenyl rings featuring a methylsulfonyl substituent are described, namely 3-methyl-1-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrazole, C17H16N2O2S, ethyl 1-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-carboxylate, C19H18N2O4S, and 1-[4-(methylsulfonyl)phenyl]-3-[3-(morpholino)phenoxymethyl]-5-phenyl-1H-pyrazole, C27H27N3O4S. The design of these compounds was based on celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in order to study the influence of various substituents on COX-2 and 5-lipoxygenase (5-LOX) inhibition.

Structural approach for COX-2 inhibition.

The design of selective COX-2 inhibitors is a new approach to obtain potent, anti-inflammatory drugs but with less side effects. Several families of such inhibitors were reported in literature. In this review, the drug design processes used to understand their binding mode and the origin of selectivity of these compounds are described.

A pharmacophore model for sulphonyl-urea (-cyanoguanidine) compounds with dual action, thromboxane receptor antagonists and thromboxane synthase inhibitors.

A 3D pharmacophore model was developed for original sulphonyl-urea (-cyanoguanidine) compounds and known molecules which behave both as thromboxane receptor antagonists and as thromboxane synthase inhibitors. Five recognition sites appear to be essential for this dual activity: two hydrogen bond acceptors, an anionic site, a hydrophobic group and an aromatic ring. Such a model could be used to design new leads possessing the same pharmacological profile and to improve the activity of our compounds.

Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs.

Dual COX/5-LOX (cyclooxygenase/5-lipoxygenase) inhibitors constitute a valuable alternative to classical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors for the treatment of inflammatory diseases. Indeed, these latter present diverse side effects, which are reduced or absent in dual-acting agents. In this review, COX and 5-LOX pathways are first described in order to highlight the therapeutic interest of designing such compounds.

N-tert-butyl-N'-(2-cyclohexylamino-5-nitrobenzenesulfonyl)urea, BM531, a dual-acting agent for thromboxane receptor antagonism and thromboxane synthase inhibition.

The title compound (BM531), C(17)H(26)N(4)O(5)S, has been designed for use as both a thromboxane synthase inhibitor (TXSI) and a thromboxane receptor antagonist (TXRA). We report here the X-ray crystal structure determination of the compound.

Lipid metabolism and FA composition in tissues of Eurasian perch Perca fluviatilis as influenced by dietary fats.

Eurasian perch, Perca fluviatilis, were fed a semipurified fat-free diet for 4 wk, followed by a 16% feeding supplementation of either olive oil (OO), safflower oil (SO), linseed oil (LO), or cod liver oil (CLO) as the only lipid source in each diet for 10 wk. Significant reductions in total lipid of tissues were observed (31.4% in viscera, 66.

Structural approach of the mechanism of inhibition of alpha-chymotrypsin by coumarins.

A pharmacophore associated to the inhibiton of alpha-chymotrypsin has been built based on the structural and electronic characterization of a series of coumarin derivatives.

Pyrazolidine-3,5-dione angiotensin-II receptor antagonists.

The crystal structures of three angiotensin-II receptor antagonists involving different spacer groups (CO, CONH and NHCO) between the aryl rings are presented, namely 2-[4-[(3-butyl-1,4-dioxo-2,3-diazaspiro[4.4]non-2-yl)methyl]benzoyl]benzoic acid, C(26)H(28)N(2)O(5), (I), 2-[4-[(3-butyl-1,4-dioxo-2,3-diazaspiro[4.4]non-2-yl)methyl]benzamido]benzoic acid, C(26)H(29)N(3)O(5), (II), and 2-[4-[(3-butyl-1,4-dioxo-2,3-diazaspiro[4.

Structure determination and comparison of BM567, a sulfonylurea, with terbogrel, two compounds with dual action, thromboxane receptor antagonism and thromboxane synthase inhibition.

BM567, a sulfonylurea compound whose crystal structure is here discussed and terbogrel, are both thromboxane receptor antagonists and thromboxane synthase inhibitors. In this paper, their crystallographic and electronic structures are compared and lead to new synthesis prospects among the sulfonylurea series.

Cation-pi (Na+-Trp) interactions in the crystal structure of tetragonal lysozyme.

Experimental evidence of a cation-pi interaction between a sodium cation (Na+) and the indole ring of residue Trp123 in a structure (2.0 A) of hen egg-white lysozyme is presented. The geometry of the metal ion-pi interaction observed in the protein structure (distance between the aromatic plane and the cation approximately 4 A) is consistent with geometries observed among small molecules crystal structures and quantum chemistry ab initio calculations.

Comparison of three luminescent assays combined with a sandwich hybridization for the measurement of PCR-amplified human cytomegalovirus DNA.

Identification of human tissue contaminated by cytomegalovirus is currently carried out by PCR amplification followed by measurement of the amplicons. Three luminescent detection systems undertaken after sandwich hybridization of the amplicons were compared. The sandwich hybridization takes place between a covalent linked capture probe, bound onto a plastic 96-well plate, and a biotinylated or digoxigenin-labeled detection probe.

Automated solid-phase synthesis of cyclic peptides bearing a side-chain tail designed for subsequent chemical grafting.

Recent developments in allyl chemistry and palladium solubilization allow automated continuous-flow solid-phase synthesis of cyclic or branched peptides, with specific side-chain cleavage and on-line cyclization. In this paper, we adapted the method to the synthesis of cyclic peptides bearing an anchoring tail on a side chain of the cycle. Side products were obtained with the standard procedure and an additional washing step had to be introduced in the synthesis protocol to remove side products resulting from the palladium allyl cleavage step.

Spin relaxation studies of pyrene by 13C nuclear magnetic resonance spectroscopy.

The effect of the repetition and contact times on the intensity of the magic-angle spinning (MAS) spectra of pyrene has been studied. Pyrene, like a great number of fused polyaromatic compounds, has a very large 13C longitudinal relaxation time (T1Z). When using the cross-polarization (CP) MAS technique, the optimum repetition time is 800 s.