Jo Alen

Anticonvulsant activity of bisabolene sesquiterpenoids of Curcuma longa in zebrafish and mouse seizure models

Turmeric, obtained from the rhizomes of Curcuma longa, is used in South Asia as a traditional medicine for the treatment of epilepsy. To date, in vivo studies on the anticonvulsant activity of turmeric have focused on its principal curcuminoid, curcumin. However, poor absorption and rapid metabolism have limited the therapeutic application of curcumin in humans. To explore the therapeutic potential of turmeric for epilepsy further, we analyzed its anticonvulsant activity in a larval zebrafish seizure assay. Initial experiments revealed that the anticonvulsant activity of turmeric in zebrafish larvae cannot be explained solely by the effects of curcumin. Zebrafish bioassay-guided fractionation of turmeric identified bisabolene sesquiterpenoids as additional anticonvulsants that inhibit PTZ-induced seizures in both zebrafish and mice. Here, we present the first report of the anticonvulsant properties of bisabolene sesquiterpenoids and provide evidence which warrants further investigation toward the mechanistic understanding of their neuromodulatory activity.

Artemisinin Analogues as Potent Inhibitors of In Vitro Hepatitis C Virus Replication

We reported previously that Artemisinin (ART), a widely used anti-malarial drug, is an inhibitor of in vitro HCV subgenomic replicon replication. We here demonstrate that ART exerts its antiviral activity also in hepatoma cells infected with full length infectious HCV JFH-1. We identified a number of ART analogues that are up to 10-fold more potent and selective as in vitro inhibitors of HCV replication than ART. The iron donor Hemin only marginally potentiates the anti-HCV activity of ART in HCV-infected cultures. Carbon-centered radicals have been shown to be critical for the anti-malarial activity of ART. We demonstrate that carbon-centered radicals-trapping (the so-called TEMPO) compounds only marginally affect the anti-HCV activity of ART. This provides evidence that carbon-centered radicals are not the main effectors of the anti-HCV activity of the Artemisinin. ART and analogues may possibly exert their anti-HCV activity by the induction of reactive oxygen species (ROS). The combined anti-HCV activity of ART or its analogues with L-N-Acetylcysteine (L-NAC) [a molecule that inhibits ROS generation] was studied. L-NAC significantly reduced the in vitro anti-HCV activity of ART and derivatives. Taken together, the in vitro anti-HCV activity of ART and analogues can, at least in part, be explained by the induction of ROS; carbon-centered radicals may not be important in the anti-HCV effect of these molecules.

Solvent diffusion through a non-porous crystal ‘caught in the act’ and related single-crystal-to-single-crystal transformations in a cationic dinuclear Ag(I) complex

The effect of a range of solvents on non-porous single crystals of a cyclic, dinuclear silver(I) complex with 1,3-bis(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene (bitmb) with the formula [Ag2(bitmb)2](BF4)2 (1) was investigated by single crystal X-ray diffraction studies. It allowed us to get a few snapshots of the process of solvent diffusion through the crystal, connected with a series of reversible transformations. We have isolated disolvated 2a and monosolvated 2b forms with acetonitrile, monosolvated 3b and 4b forms with acetone and ethanol, respectively, and monosolvated 4c form with ethanol which is an intermediate between 1 and 4b. Longer exposure of the crystals to solvent vapours leads to the formation of a polymeric 1D Ag(I) complex with the general formula [Agbitmb(BF4)]n (5).

2-(4-Meth-oxy-benz-yl)-4,6-diphenyl-2,5-diaza-bicyclo-[2.2.2]oct-5-en-3-one.

In the crystal structure of the title compound, C26H24N2O2, weak intermolecular C—H⋯π interactions involving the benzene of the p-methoxy benzyl group and one of the phenyl rings result in the formation of chains consisting of alternating enantiomers. Weak C—H ⋯O interactions with the methoxy O atom lead to the formation of layers, which are interlinked by further C—H⋯O interactions into a three-dimensional assembly.

Trans-Chlorido[6-chloro-4-(4-methoxy-benz-yl)-3-oxo-3,4-dihydro-pyrazin-2- yl]-bis-(triphenyl-phosphine)palladium(II)

The title compound, [Pd(C12H10ClN2O2)Cl(C18H15P)2], is the intermediate of the reduction of a 3,5-dichloropyrazinone [Loosen, Tutonda, Khorasani, Compernolle & Hoornaert (1991 ▶). Tetrahedron, 47, 9259–9268]. This species is formed by oxidative addition of coordinatively unsaturated Pd0 to the reactive 3-position of the heterocycle. The coordination around the Pd atom is square planar, with two trans PPh3 ligands. π–π interactions are observed between the centroid of the pyrazinone ring and planes of two adjacent phenyl rings, one from each PPh3 group (3.25 and 3.078 Å), stabilizing the intermediate structure. This could explain the reduced reactivity towards substitution of the Cl atom by the formate anion, resulting in poor yield of the reduced compound. 3-Substituted pyrazinones are important precursors in the synthesis of 5-aminopiperidinone-2-carboxylate (APC) systems.

3-Benzyl-5-bromo­pyrazin-2(1H)-one

In the title compound, C11H9BrN2O, the molecules are linked into R 2 2(8) dimers by paired N—H⋯O hydrogen bonds and these dimers are further stacked into columns along the c axis by π–π interactions between pyrazinone rings [centroid–centroid distance = 3.544 Å; the dihedral angle between the planes of these rings is 7.51 (16)°]. The title compound is a precursor for agents with potential use as pharmaceuticals.