Semisynthetic modifications of δ-amplexichromanol, an original tocotrienol with antitumoral properties

International audienc

Potentiating agents for protecting plants from fungal infections

This invention relates to a method for preventing, controlling or treating a fungal infection on a plant organ comprising applying to said plant organ a non-fungicidal amount or a potentiating amount of a composition comprising a potentiating agent of a plant defense molecule, in association with a phytopharmaceutical vehicl

Paradoxical effects of the topoisomerase inhibitor, ethoxidine, in the cellular processes leading to angiogenesis on EaHy.926 endothelial cells

Topoisomerase I generates transient single-stranded breaks in DNA and have the capacity to fragment the genome. Thus, this enzyme is the target for some of the most successful anticancer drugs. Ethoxidine, a benzo[c]phenanthridines derivative, was identified as a potent inhibitor of topoisomerase I. As angiogenesis is a critical step in tumorigenesis, this study was designed to test the potential effect of ethoxidine on different processes leading to neovascularisation on EaHy endothelial cells including adhesion, migration and proliferation. Ethoxidine was tested at two concentrations, 100 μM and 10 μM . VEGF (20 ng/mL) was used as control. Adherent cells were evaluated using crystal violet staining, migration using a model of wound healing. Proliferation was analyzed using CyQUANT Cell Proliferation Assay Kit. Both O2- and NO productions were assessed using electronic paramagnetic resonance technique. All the effects of ethoxidine were evaluated at 24 h treatment. Low concentration of ethoxidine promoted migration to the same extent as that produced by VEGF whereas high concentration inhibited this process. Ethoxidine significantly enhanced adhesion at similar level than VEGF at low concentration. It was without effect at high concentration. Although ethoxidine had no effect at low concentration, it significantly reduced cell proliferation at high concentration. At any concentration tested, ethoxidine did not modify basal O2- production. Interestingly, ethoxidine significantly increase NO production at low concentration but it was without effect at high concentration. As control experiment, VEGF enhanced Eahy cells NO production under the same experimental conditions. Altogether, the present study highlights paradoxical effects of ethoxidine depending on the concentration used. At low concentration, it promotes both Eahy cells migration and adhesion without any effect on proliferation. Importantly, these effects were associated with an increase of NO production. In contrast at high concentration, ethoxidine reduced Eahy cells migration and proliferation but had no effect neither on adhesion nor NO release. Of note is the fact that ethoxidine did not alter endothelial cells oxidative stress at any concentration tested. Thus, these data underscore the potential anti-tumoral property of ethoxidine at high concentration and endothelial cells in the present study. The property of ethoxidine in inhibiting proliferation in both cell type probably account for its high antitumor activity

Studies on the reactivity of a tertiary allylic alcohol in an acetophenonic series, a model for natural products synthesis

The synthesis of benzopyranic simplified analogues of dibenzopyranic natural compounds is described, together with the access to a precursor of a new furobenzopyranic natural product. These natural products have anti-cancer activity. The 1,3-diacetoxy-2-acetyl-4-(3-hydroxy-3-methylbut-1-enyl)benzene synthone is used as a common precursor to these structures

Novel Cytotoxic 4-Phenylfuranocoumarins from Calophyllum dispar

Eight new 4-phenylfuranocoumarins (1−8) have been isolated from the stem bark and the fruits of Calophyllum dispar, together with three known coumarins. The structures of 1−8 were established by means of spectroscopic analysis, including extensive 2D NMR studies. Some of these furanocoumarins exhibited significant cytotoxic activity against KB cells

Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors

Application of our original photooxidation–reduction methodology to prenylated dihydroxycoumarin and trihydroxyxanthone compounds led to the corresponding ortho-(2-hydroxy-3-methylbut-3-enyl)phenol derivatives with yields ranging from 8 to 65%. In most of the reported experiments, the oxidation products distribution, after the photooxygenation step, was controlled by the competition between the large group effect and the stabilising phenolic assistance effect. We also showed that ortho-(3-hydroxy-3-methylbut-1-enyl)phenol derivatives could be considered as biogenetic precursors of 2,2-dimethylbenzopyranic structures

Hydroxamate, a key pharmacophore exhibiting a wide range of biological activities

Naturally occurring hydroxamic acid derivatives are biosynthesized by microorganisms (siderophores) and plants (benzoxazinoids). Recent developments in drug discovery have highlighted the numerous biological and pharmacological properties that the hydroxamic acid function may possess, leading to therapeutic applications. These properties may be explained by its ability to chelate metals via the presence of two oxygen atoms. Their pharmacological activities can be divided into three groups. The first concerns the ability of these hydroxamic acid derivatives to scavenge metals (particularly iron), which leads to antioxidant, antimicrobial and metal detoxification activities. The latter is largely used to treat iron overload in patients. The second group of activities is related to their ability to inhibit metallo-enzymes, which gives them a wide range of pharmacological effects: antimicrobial, anti-inflammatory and antitumor. The third group is linked to the capacity of these compounds to generate nitric oxide, which confers hypotensive activity. However, hydroxamates exhibit relatively low stability in vivo, which can be overcome by the synthesis of appropriately designed analogs. For this purpose, many different strategies have been proposed. In this review, we compare and discuss the various synthetic pathways used to obtain the most complex of them, the N-substituted hydroxamic acids. We conclude that among numerous protocols reported so far, the direct N-substitution of hydroxamic acids, the acylation of the appropriate N-O derivative and the direct oxidation of the corresponding amide allow for the synthesis of a wide range of new biologically active compounds