Yves Champavier

Effects of phytoestrogens on aromatase, 3β and 17β-hydroxysteroid dehydrogenase activities and human breast cancer cells

Isoflavones and others phytoestrogens have been suggested to be anticarcinogenic. Anti-aromatase, antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there is a reduced incidence of breast cancer associated with diet. In this study, we explored some mechanisms by which they can exert cancer-preventive effects. Phytoestrogens were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. We found that isoflavonoids and compounds which presented the phenolic B ring in the 3 position on the pyran ring preferentially inhibited 3beta-HSD and/or 17beta-HSD activities than aromatase activity. We also evaluated their interactions with the estrogen receptor using a stably transfected human breast cancer cell line (MVLN). On the other hand phytoestrogens were evaluated for their effects on the proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions or/and substituents essential for these different activities. However, at high concentrations it seems that some phytoestrogens exert their protection against breast cancer through other estrogen-independent mechanisms.

Norterpenoid and sesquiterpenoid glucosides from Juniperus phynicea and Galega officinalis

Abstract Four norterpenoid glucosides have been characterized along with a sesquiterpenoid glucoside from the aerial parts of Juniperus phynicea and Galega officinalis . Among these five compounds, two norterpenoids which are 3-oxo-a-ionol glucosides named junipeionoloside and 6-hydroxy-junipeionoloside are new natural products. These new norterpenoids were isolated from Juniperus phynicea together with an other known norterpenoid glucoside: roseoside and a sesquiterpenoid glucoside: dihydrophaseic acid 4′- O - β - d -glucopyranoside. We also have identified from Galega officinalis a rare norterpenoid glucoside: dearabinosyl pneumonanthoside.

Uncommon chlorinated xanthone and other antibacterial compounds from the lichen Cladonia incrassata.

Bioassay-guided fractionation of an extract of the lichen Cladonia incrassata against Staphylococcus aureus led to a novel compound, 1,5-dihydroxy-2,4,6-trichloro-7-methylxanthone (1), along with six known compounds: (-)-usnic acid (2), didymic acid (3), condidymic acid (4), squamatic acid (5), thamnolic acid (6), and prasinic acid (7). Didymic, condidymic, and prasinic acids were isolated for the first time from C. incrassata. Didymic, condidymic, and (-)-usnic acids were active against S. aureus (a minimum inhibitory concentration of 7.5 µg/mL).

Chelation-controlled regioselective alkylation of pyrimidine 2'-deoxynucleosides

Protection-deprotection steps, which are usually needed for regioselective alkylation of pyrimidine deoxynucleosides, can be avoided by choosing the appropriate solvent. The combined effects of low dielectric constant and possible sodium chelation by pyrimidine nucleosides may account for the unexpected regioselectivity observed in THF.

Radiolytic transformation of 2,2',4'-trihydroxychalcone.

Abstract Mokrini, R., Trouillas, P., Kaouadji, M., Champavier, Y., Houée-Lévin, C., Calliste, C. A. and Duroux, J. L. Radiolytic Transformation of 2,2′,4′-Trihydroxychalcone. Radiat. Res. 165, 730–740 (2006). Radiolysis of 2,2′,4′-trihydroxychalcone, a natural antioxidant present in fruit and vegetables, was performed in ethanol in the absence or in the presence of dioxygen. The degradation process of chalcone was followed in deaerated solution by HPLC, NMR, FAB-LSIMS mass spectroscopy and analytical TLC. Under anaerobic conditions, six new products (three couples of diastereoisomers) were identified. Four of them kept the chalcone skeleton with OCH2CH3, CH(OH)CH3 and H substitutions on Cα and Cβ. Thus the target was the α-β double bond on which ethanol radicals were added. The two other compounds were formed in a second stage and exhibited a cyclization between the substituent on Cβ and the carbonyl group. In the presence of dioxygen, these reactions were prevented and chalcone was protected. This study was the first step toward understanding of the behavior chalcone in irradiated fruits and vegetables.

Lysine Analogue of Polymyxin B as a Significant Opportunity for Photodynamic Antimicrobial Chemotherapy

In order to highlight the potential of photodynamic antimicrobial chemotherapy in case of infections by antibiotic resistant-strains, a new antimicrobial peptide conjugate has been synthesized, consisting of a derivative of polymyxin B and a cationic porphyrin covalently attached together to a spacer. A polymyxin-derived moiety was subjected to a primary structural modification in the replacement of four diaminobutyrate residues with lysine ones. This modification was done in order to strongly reduce bactericidal activity, with the aim to eliminate the potential rise of polymyxin-resistant strains. Despite this modification, this new conjugate displayed a strong photobactericidal activity against Gram-positive as well as Gram-negative bacteria. It was further shown that this conjugate was able to strongly stick to the cell walls of either kind of strain, thus helping to inactivate bacteria through the production of reactive oxygen species under light irradiation.

Reactivity of Chalcones with 1-Hydroxymethyl Radicals

Abstract Mokrini, R., Trouillas, P., Kaouadji, M., Champavier, Y., Houée-Lévin, C., Calliste, C. A., Fagnère, C. and Duroux, J. L. Reactivity of Chalcones with 1-Hydroxymethyl Radicals. Radiat. Res. 166, 928–941 (2006). Reactivity of chalcones with reactive species issued from methanol radiolysis was investigated in the absence or presence of dioxygen. Chalcones are natural antioxidants that are present in fruit and vegetables. Their degradation in the radiolysed solutions was followed by HPLC, NMR, FAB-LSIMS mass spectroscopy and analytical TLC in deaerated solution. Among the 18 identified radiolytic compounds, 16 were new. The formation of the radiolytic products was not influenced by A- and B-ring substitutions. To explain the degradation process, we thus suggested that the primary step was an attack of the α,β-double bond by the 1-hydroxymethyl radical, either at Cα or at Cβ. This step was followed by addition, cyclization or bond dissociations. Different chemical pathways were discussed that implicate the reactive species issued from methanol radiolysis. This paper highlights the relative importance of the different radical species, especially the carbon-centered radical, 1-hydroxymethyl (HMR) and the corresponding oxygen-centered isomer. In addition, an interesting unusual role of dioxygen should be noted; indeed, in the presence of dioxygen, degradation of chalcones was inhibited.

New Acyclonucleosides: Synthesis and Anti-HIV Activity

The synthesis of new acyclic nucleosides is described. These syntheses were accomplished by various methods: glycosylation, selective or total deprotection, oxidation/reduction, chlorination or azidation of hydroxyl groups. The compounds were characterized with NMR, mass and IR spectroscopy. Antiviral properties of these compounds were evaluated on HIV-1 infected cell lines.

A highly efficient, solvent-free and energy-effective method of cellulose acetylation

Abstract Acetylation of cellulose by acetic anhydride was found to be catalysed quantitatively by iodine under solvent-free conditions at room temperature. Cellulose acetates were characterised by 1H NMR spectroscopy.

Cytochalasin E in the lichen Pleurosticta acetabulum. Anti-proliferative activity against human HT-29 colorectal cancer cells and quantitative variability

A biological screening of sixteen lichen extracts on human HT-29 colorectal cancer cells, led to the selection of Pleurosticta acetabulum, a lichen widely present in tree barks in Europe. Bioguided purification of the acetonic extract resulted in the isolation of cytochalasin E, a common fungal metabolite. This compound is responsible for the anti-proliferative activity of the extract. Its presence in lichens is reported here for the first time. LC-MS quantitation of cytochalasin E in different samples of P. acetabulum demonstrated quantitative variations of cytochalasin E production in the lichen and especially high concentrations in apothecia.