One-pot synthesis of organophosphate monoesters from alcohols

AbstractA one-pot procedure for the phosphorylation of alcohols provides the corresponding phosphate monoesters in improved yields. The protocol features the use of tetrabutylammonium hydrogen phosphate and trichloroacetonitrile, followed by purification of the crude product by flash chromatography on silica gel. The final step, cation exchange chromatography, affords the organophosphates as ammonium salts that are usually required for biochemical applications. The mechanism appears to be phosphate rather than alcohol activation by trichloroacetonitrile

In vitro anticancer evaluation of novel triphenyltin(IV) compounds with some N-acetyl-S-naphthoquinonylcysteine derivatives

Triphenyltin(IV) compounds with naphthoquinone derivatives containing N-acetylcysteine, N-acetyl-S-(3,4-dihydro-3,4-dioxo-1-naphthyl)cysteine (1,2-NQC), 1, and N-acetyl-S-(1,4-dihydro-1,4-dioxo-2-naphthyl)cysteine (1,4-NQC), 2, were synthesized and characterized by elemental microanalysis, IR, multinuclear (H-1, C-13, Sn-119) NMR spectroscopy as well as HR-ESI mass spectrometry. With the aim of in vitro anticancer activity determination of ligand precursors and novel synthesized organotin(IV) compounds against human cervix adenocarcinoma (HeLa), human colon carcinoma (HT-29) and melanoma carcinoma cell line (B16F10), MTT colorimetric assay method was applied. The results indicate that synthesized compounds exhibited remarkable antiproliferative activity toward all tested cell lines with IC50 in the range from 0.17 to 0.87 mu M. Complex 1 showed the greatest activity against HT-29 cells, with IC50 value of 0.21 +/- 0.01 mu M, 119 times better than cisplatin, while complex 2 demonstrated the highest activity toward HeLa cells, IC50 = 0.17 +/- 0.01 mu M, which is similar to 26 times better than cisplatin

Squalene and amentoflavone from Antidesma laciniatum

Squalene, (2E, 7x,11x)-phyt-2-en-1-ol and amentoflavone have been isolated from the extract of the leaves of Antidesma laciniatum. Their structures were elucidated using spectroscopic methods. This is the first report of these compounds from Antidesma species.   KEY WORDS: Antidesma laciniatum, Euphorbiaceae, Squalene, Amentoflavone, (2E, 7x,11x)-Phyt-2-en-1-ol  Bull. Chem. Soc. Ethiop. 2006, 20(2), 325-328

Enzymatic C–C-Coupling Prenylation: Bioinformatics – Modelling – Mechanism – Protein-Redesign – Biocatalytic Application

The functional role of isoprenoids and especially enzymatic prenylation in nature and human application is briefly covered, with the focus on bioinformatical, mechanistical and structural aspects of prenyltransferases and terpene synthases. These enzymes are as yet underrepresented but perspectively useful biocatalysts for C–C couplings of aromatic and isoprenoid substrates. Some examples of the successful use in chemoenzymatic synthesis are given including an application for the otherwise difficult synthesis of Kuhistanol A. Computational structure-based site-directed mutagenesis can be used for rational enzyme redesign to obtain altered substrate and product specificities, which is demonstrated for terpene cyclases

Anti-Inflammatory activity of a polyphenolic extract from Arabidopsis thaliana in in vitro and in vivo models of Alzheimer's Disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aβ) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD. Here, we investigated the effects of a polyphenolic extract of Arabidopsis thaliana (a plant belonging to the Brassicaceae family) on inflammatory response induced by Aβ. BV2 murine microglia cells treated with both Aβ25⁻35 peptide and extract showed a lower pro-inflammatory (IL-6, IL-1β, TNF-α) and a higher anti-inflammatory (IL-4, IL-10, IL-13) cytokine production compared to cells treated with Aβ only. The activation of the Nrf2-antioxidant response element signaling pathway in treated cells resulted in the upregulation of heme oxygenase-1 mRNA and in an increase of NAD(P)H:quinone oxidoreductase 1 activity. To establish whether the extract is also effective against Aβ-induced neurotoxicity in vivo, we evaluated its effect on the impaired climbing ability of AD Drosophila flies expressing human Aβ1⁻42. Arabidopsis extract significantly restored the locomotor activity of these flies, thus confirming its neuroprotective effects also in vivo. These results point to a protective effect of the Arabidopsis extract in AD, and prompt its use as a model in studying the impact of complex mixtures derived from plant-based food on neurodegenerative diseases

Computational Studies and Biosynthesis of Natural Products with Promising Anticancer Properties

We present an overview of computational approaches for the prediction of metabolic pathways by which plants biosynthesise compounds, with a focus on selected very promising anticancer secondary metabolites from floral sources. We also provide an overview of databases for the retrieval of useful genomic data, discussing the strengths and limitations of selected prediction software and the main computational tools (and methods), which could be employed for the investigation of the uncharted routes towards the biosynthesis of some of the identified anticancer metabolites from plant sources, eventually using specific examples to address some knowledge gaps when using these approaches

Comparison of impurity profiles of Lipiblock® vs. Orlistat using HPLC and LC-MS/MS

Comparative HPLC-UV and LC-MS/MS studies of impurity profiles of a reference sample (Xenical®, F. Hoffmann-La Roche Ltd., Switzerland) vs. generic (Lipiblock®, EMS-Sigma Pharma, a generic drug) were carried out with ethanol extracts of commercial samples. The generic formulation contained higher levels of common impurities as well as a considerable number of impurities not found in the reference product. The detected impurity profile of Lipiblock® revealed that it most likely is based on fermentation. Since the effect of the impurities is unknown, at this point fully synthetic Xenical® appears to offer a better safety margin than Lipiblock® which, however, compares quite well to other generic formulations.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae

The study presented here aims to elucidate the effects of emodin (EO = 1,3,8-trihydroxy-6-methylanthraquinone) in its free form and when loaded into a mesoporous silica nanocarrier SBA-15 (→ SBA-15|EO) on the activities of the main antioxidative enzymes, superoxide dismutase, catalase, glutathione S-transferase, and glutathione reductase, in larvae of a polyphagous insect pest, the browntail moth Euproctis chrysorrhoea (L.). The results show that only SBA-15|EO upregulates the activities of the tested antioxidative enzymes. These results point to significant differences in the effectiveness of the compound in the free versus the loaded form

Ion Homeostasis Response to Nutrient-Deficiency Stress in Plants

A crucial feature of plant performance is its strong dependence on the availability of essential mineral nutrients, affecting multiple vital functions. Indeed, mineral-nutrient deficiency is one of the major stress factors affecting plant growth and development. Thereby, nitrogen and potassium represent the most abundant mineral contributors, critical for plant survival. While studying plant responses to nutrient deficiency, one should keep in mind that mineral nutrients, along with their specific metabolic roles, are directly involved in maintaining cell ion homeostasis, which relies on a finely tuned equilibrium between cytosolic and vacuolar ion pools. Therefore, in this chapter we briefly summarize the role of the ion homeostasis system in cell responses to environmental deficiency of nitrate and potassium ions. Special attention is paid to the implementation of plant responses via NO3− and K+ root transport and regulation of ion distribution in cell compartments. These responses are strongly dependent on plant species, as well as severity and duration of nutrient deficiency