Serge Moreau

Isolation and structure (X-ray analysis) of marcfortine A, a new alkaloid from Penicillium roqueforti

The structure of marcfortine A, a novel alkaloid isolated from Penicillium roqueforti, has been established by X-ray analysis; two minor alkaloids, marcfortine B and C, as well as the previously known roquefortine have also been isolated.

Proton Nuclear Magnetic Study of Bistramide A, a new cytotoxic drug isolated from Lissoclinum Bistratum Sluiter

Abstract Modern two-dimensional NMR techniques have been used here in order to study the structure of a recently isolated cytotoxic drug, bistramide A. Mass spectroscopy indicated a M r of 704 corresponding to an apparent molecular formula of C 40 H 68 N 2 O 8 . All structural information was obtained from 1 H and 13 C NMR. 1 H- 1 H and 1 H- 13 C COSY in combination with relayed 1 H- 1 H- 13 C COSY and 1 H- 13 C COLOC were used for obtaining all crucial connectivies required for determining the partial structure of this natural product.

A nuclear magnetic resonance study of the interactions of antimalarial drugs with porphyrins

Haematins (hydroxyferriprotoporphyrin IX) constitute a possible receptor for antimalarial drugs such as chloroquine or quinine. This paper reports the study of the interactions of these two molecules with two tetrapyrrole (haematin and uroporphyrin I) by 1H-NMR spectroscopy. This method provided us with the geometry of the interactions in aqueous medium. The interaction consists of a close stacking of the porphyrin ring and the quinoleine moiety of the drugs. Using a porphyrin ring current model it was possible to reach the spatial relationships of the interacting species. It was concluded that hydrophobic forces play a key role in the interaction. The porphyrin plane can accommodate wide structural variations of the interacting species, leading to a weak specificity. The consequences on the mode of action of antimalarial drugs are discussed.

Structures of marcfortine B and C (X-ray analysis), alkaloids from

Resume Marcfortine B and C are minor alkaloids isolated from the mycelium of Penicillium roqueforti . The structure of marcfortine B was established by spectral means and that of marcfortine C by X-ray diffraction analysis.

Interactions de la chloroquine avec la ferriprotoporphyrine IX: Étude par résonance magnétique nucléaire

Chloroquine is still the antimalarial drug which is the most utilized. Nevertheless the molecular mode of action of this drug is not very well understood. When mouse erythrocytes injected with Plasmodium berghei are exposed to chloroquine, the first biochemical event is rapid accumulation of the drug. This process is energy dependent, saturable and competitively inhibited by drugs of the same therapeutic class (Quinine, Amodiaquine, Mefloquine). Receptors for chloroquine have been proposed for the process of accumulation. The nature of the chloroquine receptor is presently the subject of debates. The latest hypothesis proposed by Chou and coll. [12], is that ferriprotoporphyrin IX, formed by the degradation of hemoglobin by the parasite, binds to chloroquine with a dissociation constant of 3.5.10(-9) M. We studied here the molecular interactions between these two species by Proton Nuclear Magnetic Resonance in order to elucidate the nature and the geometry of were undertaken. The perturbations of the NMR spectra of chloroquine (10(-2) M) induced by addition of hematin or hemin were measured. Two types of measures were undertaken. The first study carried out in organic solvent (DMSO) has shown that the interaction occurred between the acidic functions of hemin and the side-chain nitrogen of chloroquine. The iron atom was not implicated in this process. The second study carried out in aqueous medium (phosphate buffer; 0.1 M; pH = 7) allowed us to demonstrate that chloroquine is able to intercalate into a polymer of hematin. The quinoleic nucleus of chloroquine was intercalated between two dimers of hematin as shown by the broadening of the signal of the quinoleic protons due to very large increase in the correlation time. Finally it was shown that chloroquine is associated as a dimer in aqueous medium by hydrophobic interactions. The association constant is 5.5 M-1.

DNA triplex stabilization property of natural anthocyanins.

The DNA triplex stabilization property of seven natural anthocyanins (five monoglucosides and two diglucosides) has been measured by the mean of triplex thermal denaturation experiments. We have noticed a difference between the diglucosides that do not modify this melting temperature and the monoglucosides (namely 3-O-beta-D-glucopyranoside of malvidin, peonidin, delphinidin, petunidin and cyanidin) which present a weak but significant stabilizing effect. It appears clearly that the difference between the two series could be due to the supplementary sugar moiety at the 5 position for the diglucosylated compounds, that would make them too crowded to allow interaction with the triplex. Among the monoglucoside series, the most active compounds are the only ones to embody a catechol B-ring in their structure that could be important for such an interaction. The need to have pure and fully characterized compounds to run these measurements, made it possible for us to unambiguously assign the 1H and 13C NMR spectra with the help of 2D NMR experiments. Thus, missing data of compounds not totally described earlier, are provided herein.

TRIPLEX STABILITY OF OLIGODEOXYNUCLEOTIDES CONTAINING SUBSTITUTED QUINAZOLINE-2,4-(1H,3H)-DIONE

Triple helical structures can be observed between double-stranded nucleic acids and a third strand through the formation of Hoogsteen hydrogen bond. We report here the use of quinazoline-2,4-dione derivatives as substitutes for thymine in TA*T triplets. The synthesis and the characterization of monochloro derivatives of quinazoline-2,4-dione as well as 5-fluoro and 6-nitro substituted quinazoline rings are described. The ability of the various modified bases to promote the formation of triplexes was reached by thermal denaturation studies.

Use of the Fluorescent Nucleoside Analogue Benzo[g]quinazoline 2′-O-Methyl--D-ribofuranoside to Monitor the Binding of the HIV-1 Tat Protein or of Antisense Oligonucleotides to the TAR RNA Stem-Loop

The Tat protein is an essential trans-activator of HIV gene expression. It interacts with its RNA recognition sequence, the trans-activation responsive region TAR, as well as cellular factors. These interactions are potential targets for drug discovery against HIV infection. We have developed a new and sensitive assay for the measurement of Tat binding to TAR in solution under equilibrium conditions based on the change of fluorescence of the base analogue benzo[g]quinazoline-2,4(1H,3H)-dione (BgQ) incorporated into the chemically synthesized model TAR stem-loop 2 to which was added Tat-[37-72] peptide (3). The results show that Tat-TAR binding strength is 2 – 3-fold stronger than has previously been determined by mobility-shift analysis. Changes of fluorescence were used also to measure the binding of antisense 2′-O-methyloligonucleotides to TAR 2.

Antioxidant properties of natural hydroquinones from the marine colonial tunicate aplidium californicum

Antioxidant prenylated hydroquinones and non active chromene or chroman extracted from the marine colonial tunicate Aplidium californicum have been studied in order to throw some light on their biological activity. It has been found that the active compounds inhibit superoxide anion production in rat alveolar macrophages and in the xanthine/xanthine oxidase system. The antioxidant activity may be ascribed rather to a direct reaction of the superoxide anion with the hydroquinones than to an enzymatic inhibition or a membrane signal transfer. A physiological activity close to that of alpha tocopherol can be considered.

The linkage of 4-O-methyl-l-galactopyranose in the agar polymers from Gracilaria verrucosa☆

Abstract 4- O -Methyl- l -galactopyranose was found in agar preparations from Gracilaria verrucosa . Its content varied with the culture conditions and with the tissue age. Highly substituted portions having this residue were obtained by enzymic degradation with β-agarase I. Permethylation analysis and 13 C-n.m.r. spectroscopy demonstrated the linkage of this sugar to O-6 of the 3- O -linked- d -galactopyranose units. The definition of agar should take into account this occurrence of 4- O -methyl- l -galactose side groups.