Carbonyl-scavenging drugs & protection against carbonyl stress-associated cell injury.

This mini-review highlights the chemical and cytoprotective properties of various hydralazine analogues that block the induction of cell death by acrolein, a highly toxic contributor to "carbonyl stress" during a diverse range of human diseases. Recent work on the action of hydralazine against various carbonyl-mediated pathologies is also reviewed.

Mechanistic investigations on the reaction between 1,2-dioxines and bulky stabilized phosphorus ylides: an efficient route to closely related cyclopropane stereoisomers.

The bulky stabilized ylides (2a-d) react with a range of 1,2-dioxines (1a-d) to afford the diversely functionalized cyclopropanes 7 in excellent yield and diastereomeric excess. This is in direct contrast to the situation when nonbulky ester ylides are utilized which results in a completely different cyclopropyl series. Through a combination of isolation, spectroscopic, temperature, and deuterium and additive effects studies, the mechanism of cyclopropane formation from this second pathway can be proposed. Importantly, enolate quenching of the intermediate 1-2lambda(5)-oxaphospholanes 4 prior to collapse results in an equilibrium mixture of intermediates 10 and 11 which have been fully characterized, and their formation is primarily a result of the steric bulk of the stabilized ester ylide. These intermediates (10/11) then collapse further and result in formation of the observed closely related cyclopropyl stereoisomers 7 and 8. Moreover, the addition of LiBr to these reactions allows for the control of which of the two possible cyclopropanation pathways will be dominant. Finally, optimal protocols that demonstrate the potential of this new cyclopropanation methodology for the ready construction of closely related cyclopropyl stereoisomers are presented.

In vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus.

Chrysophanic acid (1,8-dihydroxy-3-methylanthraquinone), isolated from the Australian Aboriginal medicinal plant Dianella longifolia, has been found to inhibit the replication of poliovirus types 2 and 3 (Picornaviridae) in vitro. The compound inhibited poliovirus-induced cytopathic effects in BGM (Buffalo green monkey) kidney cells at a 50% effective concentration of 0.21 and 0.02 microgram/ml for poliovirus types 2 and 3, respectively. The compound inhibited an early stage in the viral replication cycle, but did not have an irreversible virucidal effect on poliovirus particles. Chrysophanic acid did not have significant antiviral activity against five other viruses tested: Coxsackievirus types A21 and B4, human rhinovirus type 2 (Picornaviridae), and the enveloped viruses Ross River virus (Togaviridae) and herpes simplex virus type 1 (Herpesviridae). Four structurally-related anthraquinones--rhein, 1,8-dihydroxyanthraquinone, emodin and aloe-emodin were also tested for activity against poliovirus type 3. None of the four compounds was as active as chrysophanic acid against the virus. The results suggested that two hydrophobic positions on the chrysophanic acid molecule (C-6 and the methyl group attached to C-3) were important for the compound's activity against poliovirus.

Antiviral flavonoid from Pterocaulon sphacelatum, an Australian Aboriginal medicine.

The antipicornaviral activity of an ethanolic extract of the green aerial parts of the Australian plant Pterocaulon sphacelatum (Labill.) Benth. & Hook. f. ex F. Muell. has been investigated. This plant has been a favoured traditional medicine, used for the treatment of colds by the Australian Aboriginal people. Antiviral activity-guided fractionation of the extract of P. sphacelatum using an inhibition of poliovirus-induced cytopathic effect assay, has yielded the antiviral flavonoid chrysosplenol C (3,7,3'-trimethoxy-5,6,4'-trihydroxyflavone). This compound is a 4'-hydroxy-3-methoxyflavone, one of a group of compounds known to be potent and specific inhibitors of picornaviral replication. These compounds inhibit the replication of rhinoviruses, the most frequent causative agent of the common cold. The coumarin 6,7,8-trimethoxycoumarin was also isolated from the ethanolic extract.

Characterisation and in vitro cytotoxicity of triorganophosphinegold(i) 2-mercaptobenzoate complexes.

The preparation and full NMR ((1)H, (13)C and (31)P) characterisation of three [R(3)PAu(2mba)] complexes, Where R = Et, Ph and Cy, and 2mba is the anion derived from 2-mercaptobenzoic acid is reported. An interesting solvent dependence in the (1)H spectra is rationalised in terms of competing intra- and inter-molecular hydrogen bonding. An X-ray analysis of the [Ph(3) PAu(2mba)] species reveals a linear P-Au-S arrangement and association in the lattice via the familar carboxylic acid dimer motif. The in Vitro cytotoxicity against seven human tumout lines is also described. The complexes display moderate to very high activity. Particularly noteworthy is their greater activity against the H226 cell line (non-small cell lung cancer) compared with that displayed by a range of cytotoxic drugs.