Separation and analysis of glycyrrhizin, 18beta-glycyrrhetic acid and 18alpha-glycyrrhetic acid in liquorice roots by means of capillary zone electrophoresis

Glycyrrhizin is the main active compound of Glycyrrhiza glabra root extracts; according to recent studies, glycyrrhizin and its aglycon, glycyrrhetic acid, have interesting therapeutic properties. A new capillary electrophoretic method has been developed for the separation and quantification of glycyrrhizin, beta-glycyrrhetic acid and its isomer a-glycyrrhetic acid. Separation of the analytes was achieved in less than 3 min on a fused silica capillary, by injecting the samples at the short end of the capillary (effective length: 8.5 cm). The background electrolyte was composed of pH 10.0 carbonate buffer, methanol and ethylene glycol (80/10/10) and contained 0.4% beta-cyclodextrin; indomethacin was used as the internal standard. Diode array detection was used, with quantitative assays carried out at 254 nm. Linearity was found over the 5-200 and 2.5-100 microg mL(-1) concentration ranges for glycyrrhizin and glycyrrhetic acid, respectively. This method has been applied to the determination of the analytes in different matrices (liquorice roots and commercial confectionery products), and to the purity control of beta-glycyrrhetic acid obtained from the hydrolysis of glycyrrhizin. When analysing beta-glycyrrhetic acid and its epimer in roots, the samples were purified by means of a suitable solid-phase extraction (SPE) procedure with Oasis HLB cartridges, which granted good selectivity, eliminating matrix interference.     

Ultrasound effects on the Mn(III) - promoted addition of amidoalkyl radicals to olefins

Amidoalkyl radicals, generated from amides by Mn(OAc)₃ in acetic acid react with phenyl substituted alkenes to generate five-membered lactones or lactams. Ultrasound at ambient temperature significantly accelerates these single electron transfer reactions even when compared with conventional conditions under reflux or simple mechanical stirring. In some cases sonication leads to unusual products.     

Chemometric studies in the Lagoon of Venice, Italy. Annual evolution of sulphur species and relationship to biogeochemical cycles in lagoon water

During the period March 1997-March 1998 dimethyl sulphide (DMS), dimethylsulphoniopropionate (DMSP) and carbon disulphide (CS2) were determined weekly in the water of the Lagoon of Venice, Italy (at three stations located in the Giudecca Canal, the San Secondo Canal and the Rio di San Nicolò). At the same time, the following hydrological and biological variables were also measured: tide height, temperature, transmittance, fluorescence, pH, salinity, chlorinity, sulphate, ammonia, nitrite, nitrate, phosphate, silicate, chlorophyll a, phaeopigments, phytoplankton (abundance and biomass). Principal component analysis (PCA), applied as a dimension reduction tool, made it possible to summarize multivariate information in a small number of components, which highlighted the relationships between the temporal evolutions of the sulphur compounds with hydrological and biological variables in the seasonal biogeochemical cycle of the lagoon. In particular the overall temporal cycle, which begins with the development of biological activity in late winter and spring, followed by the predominance of degradation processes during the late summer and the remineralization of nutrients in autumn, is clearly described in the plane of the first two principal components, together with the interrelationships between all the relevant variables.     

Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers

Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the α_vβ₃‐integrin ligand cyclo[DKP–RGD]‐CH₂NH₂ ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified α_Vβ₃‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (α_Vβ₃?) and its subclone CCRF‐CEM α_Vβ₃ (α_Vβ₃+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM α_Vβ₃ versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload.     

Degradation of the antiviral drug oseltamivir carboxylate in surface water samples

Numerous studies have documented that a wide number of pharmaceuticals used in human and veterinary medicine have the potential to enter the aquatic ecosystem. The antiviral prodrug oseltamivir phosphate has received recent attention with regard to its possible use against the highly pathogenic H5N1 virus. This preliminary laboratory study investigated the persistence of the active antiviral drug, oseltamivir carboxylate (OSC), in water samples taken from an irrigation canal. After an initial rapid decrease, OSC concentrations slowly decreased during the remaining incubation period. Approximately 65% of the initial OSC amount remained in water at the end of the 36-day incubation period. A small amount of OSC was lost both from sterilized water and from sterilized water/sediment samples, suggesting a significant role for microbial degradation. Stimulating microbial processes by the addition of sediments resulted in reduced OSC persistence. Presence of OSC (1.5?µg?mL^?1) did not significantly affect the metabolic potential of the water microbial population, estimated by glyphosate and metolachlor mineralization. In contrast, OSC caused an initial transient decrease in the size of the indigenous microbial population of water samples.