R. Hocquemiller

Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis

The stem barks of Pera benensis are employed by the Chimane Indians in the Bolivian Amazonia as treatment of cutaneous leishmaniasis caused by the protozoan Leishmania braziliensis. The chloroform extracts containing quinones were found active against the promastigote forms of Leishmania and the epimastigote forms of Trypanosoma cruzi at 10 micrograms ml-1. The activity guided fractionation of the extract by chromatography afforded active compounds. Their structures were elucidated, by spectral and chemical studies, as known naphthoquinones, plumbagin, 3,3-biplumbagin, 8-8-biplumbagin, and triterpene, lupeol. The activity in vitro of each compound was evaluated against 5 strains of Leishmania (promastigote), 6 strains of Trypanosoma cruzi (epimastigote) and the intracellular form (amastigote) of Leishmania amazonensis. The baseline drugs used were Glucantime and pentamidine (Leishmania spp.), nifurtimox and benznidazole (T. cruzi). Plumbagin was the most active compound in vitro. This study has demonstrated that Pera benensis, a medicinal plant used in folk medicine, is an efficient treatment of cutaneous leishmaniasis.

Substituted quinolines induce inhibition of proliferation of HTLV-1 infected cells.

Several quinolines were synthesized and evaluated against HTLV-1 infected cells. Some of them were able to inhibit HTLV-1 cell-growth at 10 microM. Some structure-activity relationships were observed.

Bisbenzylisoquinoline alkaloids from Guatteria boliviana (Annonaceae).

Together with known alkaloids, five new bisbenzylisoquinoline derivatives were isolated from the stem bark of Guatteria boliviana (Annonaceae), puertogalines-A 1 and -B 2, (+)-guatteboline 3, philogaline 4 and (-)-antioquine 5. Their structures were elucidated by spectrometric methods and their antiparasitic activity was evaluated in vitro on Leishmania sp., Trypanosoma cruzi and Plasmodium falciparum. Their cytotoxic activity was also measured in KB cell line.

Klaivanolide, an antiprotozoal lactone from Uvaria klaineana

Bioguided-fractionation of a CH(2)Cl(2) extract of the stems of Uvaria klaineana (Annonaceae) led to isolation of klaivanolide, a novel bisunsaturated 7-membered lactone (5-acetoxy-7-benzoyloxymethyl-7H-oxepin-2-one), together with benzyl benzoate. Klaivanolide showed potent in vitro antileishmanial activity against both sensitive and amphotericin B-resistant promastigote forms of Leishmania donovani with IC(50) values of 1.75 and 3.12 microM, respectively. The compound also showed in vitro trypanocidal activity against trypomastigote forms of Trypanosoma brucei brucei GVR 35. Its structure was established by 1D and 2D NMR and other spectroscopic techniques.

Isolation and structure elucidation of sabadelin, an acetogenin from roots of Annona muricata

Abstract A new acetogenin, sabadelin, has been isolated from the roots of Annona muricata and was characterised using tandem mass spectrometry (MS/MS). The structure determination of this compound was strengthened by epoxidation and transformation leading to a known mono-tetrahydrofuran acetogenin. Sabadelin is probably an intermediate in the biosynthetic pathway of mono-THF acetogenins, and it is proposed as a biogenetic precursor of cis -panatellin.

Triterpenes from Prunus africana bark

A chloroformic extract of barks of Prunus africana was found to contain triterpenic acids including derivatives of ursolic and oleanolic acids. Among them 24-O-trans-ferulyl-2α,3α-dihydroxy-urs-12-en-28-oic acid, an original compound, was isolated. Their structure was established by chemical and spectral analysis.

In vitro and in vivo leishmanicidal studies of Peperomia galioides (Piperaceae)

Petroleum ether and methylene chloride extracts of Peperomia galioides and three prenylated diphenols, grifolic acid, grifolin and piperogalin exhibited in vitro antileishmanial activity. During the course of infection of BALB/c mice with Leishmania amazonensis, the treatments with each of these compounds did not influence the progression of the disease.

Annosenegalin and annogalene: two cytotoxic mono-tetrahydrofuran acetogenins from Annona senegalensis and Annona cherimolia

Two new cytotoxic mono-tetrahydrofuran acetongenins, annosenegalin and annogalene, have been isolated from the cytotoxic methanolic extract of Annona senegalensis and A. cherimolia seeds. Their structures were established on the basis of 1D and 2D NMR spectroscopic techniques. Annosenegalin belongs to the rare type of C37 mono-tetrahydrofuran acetogenins, and annogalene is an olefinic acetogenin.

Antitumoral effects of squamocin on parental and multidrug resistant MCF7 (human breast adenocarcinoma) cell lines.

The antiproliferative effects of squamocin, one of the easiest annonaceous acetogenins to obtain, were studied in the parental (MCF7-S) and the multidrug resistant (MCF7-R) human breast adenocarcinoma cell lines. Squamocin inhibited proliferation of both cell lines identically, by blocking the cell cycle in the G1-phase. This inhibition was reversible in the long term. Squamocin decreased the ATP pool in both MCF7 cell lines, but did not seem to induce apoptosis. Cytotoxic activity of adriamycin was not restored in MCF7-R Pgp expressing cells by squamocin addition.

Cohibins A and B, acetogenins from roots of Annona muricata☆

Abstract Cohibins A and B, Biogenetic intermediates of acetogenins, were characterized using tandem mass spectrometry (MS/MS) from the roots of Annona muricata.