Biomedical subjects

Olivier Duval

Publications and source records attributed to Olivier Duval.

6 recordsLinked to original sources

PubMed2005

Antimalarial benzo[c]phenanthridines.

Analogues of the antimalarial alkaloid nitidine have been prepared with high potency against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. Simple modifications, using an established synthetic route, resulted in an analogue with IC(50) below 5ng/mL against a chloroquine-sensitive strain of P. falciparum. N-Ethylethoxidine had IC(50) below 30ng/mL against both chloroquine-sensitive and chloroquine-resistant strains of P. falciparum.

Animals↗

PubMed2004

Antimalarial xanthones from Calophyllum caledonicum and Garcinia vieillardii.

The antimalarial activity of 22 xanthones against chloroquino-resistant strains of Plasmodium falciparum was evaluated. Natural caloxanthone C (1), demethylcalabaxanthone (2), calothwaitesixanthone (3), calozeyloxanthone (4), dombakinaxanthone (5), macluraxanthone (6), and 6-deoxy-gamma-mangostin (7) were isolated from Calophyllum caledonicum. 1,6-dihydroxyxanthone (8), pancixanthone A (9), isocudraniaxanthone B (10), isocudraniaxanthone A (11), 2-deprenylrheediaxanthone B (12) and 1,4,5-trihydroxyxanthone (13) were isolated from Garcinia vieillardii. Moreover, synthetic compounds (14-22) are analogues or intermediates of xanthones purified from Calophyllum caledonicum (Oger J.M., Morel C., Helesbeux J.J., Litaudon M., Seraphin D., Dartiguelongue C., Larcher G., Richomme P., Duval O. 2003. First 2-Hydroxy-3-Methylbut-3-Enyl substituted xanthones isolated from Plants: structure elucidation, synthesis and antifungal activity. Natural Product Research 17(3), 195-199; Helesbeux J.J., Duval O., Dartiguelongue C., Seraphin D., Oger J.M., Richomme P., 2004. 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. Tetrahedron 60(10), 2293-2300). The relationship between antimalarial activity and molecular structure of xanthones has also been explored. The most potent xanthones (2), (3) and (7) (IC50 = c.a. 1.0 microg/mL) are 1,3,7 trioxygenated and prenylated on the positions 2 and 8.

Animals↗

PubMed2004

In vitro metabolism of ethoxidine by human CYP1A1 and rat microsomes: identification of metabolites by high-performance liquid chromatography combined with electrospray tandem mass spectrometry and accurate mass measurements by time-of-flight mass spectrometry.

Ethoxidine (N-methyl-12-ethoxy-2,3,8,9-tetramethoxybenzo[c]phenanthridinium methylsulfonate salt) is a synthetic 2-methoxy-12-ethoxy derivative of the natural alkaloid fagaronine. This new inhibitor of DNA-topoisomerase I is considered as a potential antitumor agent with higher in vitro activity than fagaronine. In order to further improve the efficiency of ethoxidine, its in vitro biotransformation by hepatic monooxygenases and the structures of its metabolites were investigated by high-performance liquid chromatography (HPLC) combined with electrospray ionization tandem mass spectrometry (ESI-MS/MS) and accurate mass measurement by time-of-flight mass spectrometry (TOFMS). When ethoxidine was incubated with BNF-treated rat liver microsomes or with cells expressing different recombinant human cytochrome P450, the same four ethoxidine metabolites (m(1)-m(4)) were detected and were formed exclusively by CYP1A1. The structures of these metabolites were assigned from ESI-MS/MS mass spectra and compared with those of ethoxidine derivatives. Accurate mass measurements of in-source ESI-TOFMS fragment ions exhibited successive neutral losses of C(2)H(4) and CO for ethoxidine and its metabolites. Whereas a 15 Da loss (methyl radical) was observed for the metabolites m(1)-m(4) containing a quaternary ammonium group, a 16 Da loss (methane) was observed for ethoxidine and could have resulted from the presence of two methoxy groups at adjacent positions (C-2 and C-3). The proposed oxidative modifications of ethoxidine were further confirmed by determination of the number of exchangeable hydrogen atoms and by the proposed elemental compositions of the metabolites based on accurate mass measurements by TOFMS. Two major metabolites resulted from O-demethylation of ethoxidine; one was tentatively identified as 12-ethoxyfagaronine (m(3)) and the second as an O-demethylated ethoxidine isomer (m(4)). Two polar metabolites were shown to be O-demethylated (m(1)) and hydroxylated (m(2)) derivatives of 12-ethoxyfagaronine. When 12-ethoxyfagaronine was incubated under the same conditions as ethoxidine, m(2) was formed, thus supporting the proposal that 12-ethoxyfagaronine is the primary oxidative product of ethoxidine.

Animals↗

PubMed2004

Synthesis and antiviral effect against herpes simplex type 1 of 12-substituted benzo[c]phenanthridinium salts.

The synthesis of benzo[c]phenanthridine alkaloid derivatives is described. In vitro antiviral activity against herpes simplex type 1 (HSV1) has been investigated. Contrary to the natural product fagaronine, which did not have any activity in the HSV1 antiviral tests, four 12-alkoxy derivatives showed good activity demonstrating the importance of the 12-substitution in the structure-activity relationships.

Animals↗

PubMed2003

First 2-hydroxy-3-methylbut-3-enyl substituted xanthones isolated from plants: structure elucidation, synthesis and antifungal activity.

Two new 2-hydroxy-3-methylbut-3-enyl substituted xanthones, (+/-)-caledol 1 and (+/-)-dicaledol 2 were isolated from a dichloromethane extract of the leaves of Calophyllum caledonicum (Clusiaceae). Compounds 1 and 2 are the first 2-hydroxy-3-methylbut-3-enyl substituted xanthones isolated from natural source. Their structures were elucidated by means of combined analytical methods including HRFABMS, 1D and 2D NMR spectroscopies and also confirmed by total synthesis using biomimetic ortho-prenylphenols photooxygenation (1O2) as a key step. The antifungal activity against Aspergillus fumigatus is reported.

Aspergillus fumigatus↗

PubMed2002

Synthesis and antimalarial activity of some new 1,2-dioxolane derivatives.

The synthesis of 1,2-dioxolane derivatives in two different acetophenone series, as simplified models of natural coumarins is described. 2-Acetyl-3-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl)phenyl acetate and 2-acetyl-5-acetoxy4-(3-hydroperoxy-3-methylbut-1-enyl) phenyl acetate synthons are used as precursors to these structures. In vitro antimalarial activity of the 1,2-dioxolane derivatives has been investigated.

Acetophenones↗