Cytotoxic effects of four Caryophyllaceae species extracts on macrophage cell lines.

CONTEXT: Saponins have been reported to possess antitumor properties, to inhibit angiogenesis and to induce tumor apoptosis. OBJECTIVE: To test the possible cytotoxic effect of crude extracts from four Caryophyllaceae species including Gypsophila paniculata L., Gypsophila trichotoma Wend., Saponaria officinalis L., and Dianthus sylvestris Wulffen on cultured monocyte/macrophage cell lines. MATERIALS AND METHODS: After acid hydrolysis of the methanol-aqueous extracts, two representative prosaponins of the Caryophyllaceae, gypsogenin 3-O-glucuronide and quillaic acid 3-O-glucuronide were purified using solid-phase extraction (SPE), then identified by ultra-performance liquid chromatography-electrospray/mass spectrometry (UPLC-ESI/MS). Cytotoxic activity of the crude extracts at concentrations ranging from 0.1 to 200 µg/ml was evaluated on rat alveolar macrophage NR8383 and human monocytic THP-1 cell lines. Apoptosis was determined by measuring caspase-3 activity. RESULTS: Quantitative analysis by reversed-phase high-performance liquid chromatography (RP-HPLC) revealed a high content of gypsogenin 3-O-glucuronide in Gypsophila species roots (0.52-1.13% dry weight). At a concentration ≥10 µg/ml of crude extracts, a significant reduction of NR8383 and THP-1 cell lines viability was evidenced using the Trypan blue exclusion test. D. sylvestris extract exhibited the highest toxicity against THP-1 cells. Caspase-3 activation was evidenced after 4 and 24 h incubation of macrophages with 100 µg/ml of S. officinalis and G. trichotoma extracts, indicating apoptosis induction. DISCUSSION AND CONCLUSION: Crude extracts from the assayed species revealed cytotoxic effects toward macrophage cell lines. In Gypsophila species, gypsogenin 3-O-glucuronide derivatives could be responsible for the observed cytotoxicity. Therefore, crude extract of Caryophyllaceae is worth investigating for the potential development of agents against cancer cells.

Toxicity of Hydnora johannis Becca. dried roots and ethanol extract in rats.

AIM OF THE STUDY: Hydnora johannis Becca. (Hydnoraceae) commonly is used for the treatment of dysentery, diarrhoea, cholera and swelling tonsillitis in the folk medicine of Sudan and other African countries. This study evaluates the toxicological effects of Hydnora johannis roots on Wistar rats. MATERIALS AND METHODS: Rats were randomized into control, groups fed with 2, 10, 20% of dried roots for 8 weeks and other groups given ethanol extract (50, 100, 200 and 400mg/kg/day) through oral and intramuscularly administration for 2 weeks. Toxicity was evaluated using biochemical and histopathological assays. RESULTS: Alterations in the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, cholesterol and urea were observed. Histopathological analysis revealed that the toxic effect were mainly on the liver, kidney and spleen on all treated groups. However, the impact of the dried roots was mild compared to the ethanol extract. Remarkably, there was a drop in cholesterol level in all treatment groups suggesting the antiartherogenic effect of Hydnora johannis roots. CONCLUSION: The results from this study suggest that the powder preparation as well as ethanolic extract of Hydnora johannis roots induced toxic effect on Wistar rats. The observed toxic effect might be due to the dose and/or frequency of administration. Although in traditional medicine the extract is administrated in low dose, the results suggest the necessity of standardization of the drug.

Design, synthesis and preliminary biological evaluation of a focused combinatorial library of stereodiverse carbohydrate-scaffold-based peptidomimetics.

A focused combinatorial library of 126 mimetics of the RGD sequence based on sugar scaffolds have been rationally constructed using molecular modeling, with a particular emphasis on the stereodiversity of the library. A liquid phase, mix and divide synthesis was used, active compounds being identified by using orthogonal libraries and recursive deconvolution strategies.

1,6-anhydro-2, 3-di-O-benzyl-5C-[(R)-ethoxycarbonyl(hydroxy)methyl]-beta-L-altrofur ano se.

The crystal structure of the title compound, C(24)H(28)O(8), has been determined. The conformation of the furanose ring can be described as 58% ideal envelope (O)E conformer and 42% ideal twisted (O)T(1) conformer. The 1,3-dioxane ring adopts a chair conformation with the anhydro-O atom pointing upwards. Both phenyl rings are quasi-perpendicular to the mean plane of the furanose ring. The hydrogen bonding is intermolecular and consists of infinite chains parallel to the a axis.

Synthesis and biological testings as inhibitors of HMGCoA reductase of the seco-acid of tuckolide and its C-7 epimer.

The seco-acid of the natural macrolactone, tuckolide (decarestrictin D) and the C-7 epimer have been prepared in enantiomerically pure form from D-gluconolactone and poly(3-hydroxy butyric acid). The key steps are Horner Emmons olefination and stereoselective reduction of the resulting enone to provide both epimers at C-7. None of the seco-acids inhibit microsomal HMGCoA reductase of pea or rat liver. It may be concluded that the cholesterol biosynthesis inhibiting effect of tuckolide is unlikely to proceed via HMGCoA reductase inhibition.

Elucidation of a common structure of selective fibrinogen receptor antagonists.

In this paper, we investigate the common structural and electrostatic parameters of a series of specific inhibitors of the alpha IIb beta 3 integrin. Molecular dynamics simulations with an explicit aqueous environment led to an original theoretical pattern. Our results may suggest that the studied non-peptide alpha IIb beta 3 antagonists developed upon the Arg-Gly-Asp ubiquitous recognition sequence, in fact, should mimic the C-terminus part of the fibrinogen gamma chain. This assumption could, therefore, explain their specificity with respect to other Arg-Gly-Asp-dependent integrins.