Browsing by Autor "Fournet, A"

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[Active antihelminitic alkaloids: active in vitro against Leishmanic Tropica the protozoa involved in leishmaniasis].
(1988) Fournet, A; Muñoz, V; Manjon, A M; Angelo, A; Hocquemiller, R; Cortes, D; Cave, A; Bruneton, J
Leishmaniasis caused by protozoan Leishmania ssp., is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Leishmania ssp. (pentavalent antimony compounds, pentamidine and amphothericine B) are toxic and expensive products. Basing on the Bolivian folk medicine, we tried to find new active principles. Fourteen isoquinoline alkaloids, especially bisbenzylisoquinoline alkaloids extracted from Annonaceae, Berberidaceae, Hernandiaceae and Menispermaceae, demonstrate highly effective activity against this protozoan. Among them gyrocarpine, daphnandrine and obaberine seem to be of particular interest. The therapeutic effect was studied by biological assays on culture forms in vitro three strains of Leishmania, L. donovani, L. braziliensis (cutaneous and mucocutaneous leishmaniasis), L. mexicana amazonensis (cutaneous) and L. donovani (visceral leishmaniasis).
[ Active trypanocidal alkaloids, bisbenzylisoquinoles ii. active in vitro against trypanosoma cruzi the agent responsible for trypanosomiasis, south america].
(1988) Fournet, A; Manjon, A M; Muñoz, V; Angelo, A; Bruneton, J; Hocquemiller, R; Cortes, D; Cavé, A
Chagas disease caused by the protozoan Trypanosoma cruzi is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Trypanosoma cruzi (imidazol compounds, lampit and benznidazol) are not very convenient products. Since it is known that protozoan Trypanosoma are close to Leishmania we studied the action of 14 bisbenzylisoquinoline alkaloids, in vitro, on three strains of T. cruzi (Tulahuen, C8C11, and 1979 CL1). As in the case of Leishmania, gyrocarpine, daphnandrine and obaberine showed an interesting activity and we judge them to be worthy of in vivo assays.
Alcaloides de los frutos de Caryomene olivascens
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 1987) Fournet, A
RESUMEN. Se estudiaron los alcaloides presentes en frutos de Caryomene olivascens Barneby et Krukoff (Menispermáceas). Por desengrasado y extracción posterior con cloruro de metileno se aislaron 8 alcaloides cuaternarios: (+)coclaurina, (-)estefarina, (+)pseudopalmatina, (-)discretina, (-)govadina, (-)demetil-1 O-discretina, (-)coreximina y (-)xilopinna. No se han encontrado alcaloides bisbenzilisoquinolínicos, mayoritarios en los tallos de la misma especie.
Antileishmanial activity of a tetralone isolated from ampelocera edentula, a Bolivian plant used as a treatment for cutaneous Leishmaniasis
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 1994) Fournet, A
Abstract. The stem bark of Ampelocera edentula Kuhlm. (Ulmaceae) is used by the Chimanes Indians from Bolivia for the treatment of cutaneous leishmaniasis caused by the protozoan Leishmania braziliensis. A chloroform extract of the stem barks was found to be active against extracellular forms of Leishmania ssp. and Trypanosoma cruzi at 50 micrograms/ml. Bioassay-guided fractionation of this extract allowed us to isolate one active compound. Its structure was elucidated by spectral and chemical studies as 4-hydroxy-1-tetralone. BALB/c mice infected with L. amazonensis (PH8) or L. venezuelensis were treated one day after the parasitic infection with 4-hydroxy-1-tetralone (25 mg/kg/day) or with reference drug, Glucantime (56 mg Sbv/kg/day) for 14 days. Lesion development was the criteria used to evaluate the disease severity. 4-Hydroxy-1-tetralone was slightly less effective than the reference drug against L. amazonensis or L. venezuelensis. Single treatment near the site of infection, 14 days after infection with L. amazonensis, with 4-hydroxy-1-tetralone (50 mg/kg) was more effective than Glucantime (112 mg/kg). This study is, to our knowledge, the first to show the activity of a tetralone for the experimental treatment of New World cutaneous leishmaniasis.
Antiprotozoal activity of quinoline alkaloids isolated from Galipea longiflora, a Bolivian plant used as a treatment for cutaneous Leishmaniasis
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 1994) Fournet, A
Abstract. The stem bark of Galipea longiflora is used by the Chimane Indians in Bolivia for the treatment of cutaneous leishmaniasis produced by Leishmania braziliensis. Petroleum ether and chloroform extracts of stem, root bark and leaves were found active in vitro against Leishmania ssp and Trypanosoma cruzi at 100 µg/mL. The activity guided fractionation of the extracts by chromatography afforded 12 active compounds identified as 2-substituted quinoline alkaloids. BALB/c mice were infected with Leishmania amazonensis (strain PH8 or H-142) and treated 24 h after infection with the major alkaloids from the crude alkaloidal extract; 2-phenylquinoline and 2-n-pentylquinoline. 2-phenylquinoline was as potent as Glucantime (Rhône-Poulenc) against the strain H-142, but less active than the reference drug against the virulent strain PH8 of L. amazonensis. 2-n-pentylquinoline did not exhibit any activity. Assays of single local treatments on the rear footpad infection, 2 weeks after the parasitic inoculation, indicated an effect for 2-phenylquinoline by reducing the severity of lesion. However, this activity was found to be slightly lower than that obtained using Glucantime.
Effect of natural naphthoquinones in BALB/c mice infected with Leishmania amazonensis and L. venezuelensis
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 1992) Fournet, A
Abstract. Plumbagin, 3,3’-biplumbagin and 8,8'-biplumbagin are naphthoquinones isolated by activity-directed fractionation from a Bolivian plant; Pera benensis, used in folk medicine as treatment of cutaneous leishmaniasis caused by Leishmania braziliensis. BALB/c mice were infected with L. mexicana or L. venezuelensis and treated 24h after the parasitic infection with plumbagin (5 or 2.5mg/kg /day), 3,3'-biplumbagin, 8,8'-biplumbagin (25 mg/kg/d) or Glucantime (200 mg/kg /d). Lesion development was the criteria employed to evaluate the inhibitory effect. The bisnaphthoquinones were less potent than Glucantime against L. amazonensis and L. venezuelensis. Plumbagin and Glucantime delayed the development of L. amazonensis and L. venezuelensis. Assays of a single local treatment on footpad infection two weeks after the parasitic inoculation with L. amazonensis showed that 8,8'-biplumbagin (50mg/kg/d)was as potent as Glucantime (400 mg/kg/d).
Les chimanines, nouvelles quinoleines substituées en 2, isolées d'une plante bolivienne antiparasitaire : galipéa longiflora
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 1993) Fournet, A
ABSTRACT.-Petroleum ether and CHCI₃, extracts of stem, root bark, and leaves of Galipea longifora were found active in vitro against Leishmania sp. and Trypanosoma cruzi at 100 µg/ml. The activity-guided fractionation of the extracts by chromatography afforded thirteen active compounds identified as 2-substituted quinoline alkaloids. Four new 2-alkylquinoline alkaloids were isolated and identified from leaves or trunk bark of G. longiflora: 4-methoxy-2-n-propylquinoline [10] (chimanine A), 2-(E)-prop-1 ‘-enylquinoline [11] (chimanine B), 4- methoxy-2-(E)-prop-1’-enylquinoline [12) (chimanine C), and 2-( 1 ’,2 ’-trans-epoxypropyl)- quinoline [13] (chimanine D). These alkaloids are accompanied by eight known 2-substituted quinolines (2-9), and by one known furo-(2,3b)-quinoline alkaIoid, skimmianine [1].
The activity of 2-substituted quinoline alkaloids in BALB/c mice infected with Leishmanis donovani
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 1994) Fournet, A
Abstract. Potent antileishmanial activity has recently been described in vivo when certain 2-substituted quinoline alkaloids are administered to mice with cutaneous leishmaniasis. We now report the ahtileishmanial activity of four 2-substituted quinoline alkaloids, namely chimanine D or 2-(1',2'-trans-epoxypropyl) quinoline (I). 2-n- propylquinoline (II), 2-styrylquinoline (III) and 2-(2'-hydroxypropyl) quinoline (IV), for experimental treatment of visceral leishmaniasis in infected BALB/c mice. Subcutaneous treatment with chimanine D for 10 days at 0-54 mmol/kg per day resulted in 86.6% parasite suppression in the liver. Oral administration of 0-54 mmol/kg of 2-n-propylquinoline once daily for 5 or 10 days to L. donovani-nfected mice suppressed parasite burdens in liver by 87.8 and 99.9%. respectively. Cutaneous administration of meglumine antimonate for 10 days resulted in 97.4% parasite suppression in the liver. This study is, to our knowledge, the first to demonstrate the activity of 2-substituted quinoline alkaloids in experimental treatment of visceral leishmaniasis. Further biological and chemical studies of these products might yet prove helpful for the development of new antileishmanial drugs.