Reversing the biofilm-inducing effect of two xanthones from Garcinia mangostana by 3-methyl-2(5H)-furanone and N-butyryl-D-L homoserine lactone.

BACKGROUND: According to the WHO, 12 bacteria cause numerous human infections, including Enterobacteriaceae Klebsiella pneumoniae, and thus represent a public health problem. Microbial resistance is associated with biofilm formation; therefore, it is critical to know the biofilm-inducing potential of various compounds of everyday life. Likewise, the reversibility of biofilms and the modulation of persister cells are important for controlling microbial pathogens. In this work, we investigated the biofilm-inducing effects of xanthones from Garcinia mangostana on Klebsiella pneumoniae. Furthermore, we investigated the reversal effect of 3-methyl-2(5H)-furanone and the formation of persister cells induced by xanthones and their role in modulating the biofilm to the antibiotic gentamicin. METHODS: To analyze the biofilm-inducing role of xanthones from Garcinia mangostana, cultures of K. pneumoniae containing duodenal probe pieces were treated with 0.1-0.001 µM α- and γ-mangostin, and the biofilm levels were measured using spectrophotometry. To determine biofilm reversion, cultures treated with xanthones, or gentamicin were mixed with 3-methyl-2(5H)-furanone or N-butyryl-DL-homoserine lactone. The presence of K. pneumoniae persister cells was determined by applying the compounds to the mature biofilm, and the number of colony-forming units was counted. RESULTS: The xanthones α- and γ-mangostin increased K. pneumoniae biofilm production by 40% with duodenal probes. However, 3-methyl-2(5H)-furanone at 0.001 µΜ reversed biofilm formation by up to 60%. Moreover, adding the same to a culture treated with gentamicin reduced the biofilm by 80.5%. This effect was highlighted when 3-methyl-2(5H)-furanone was administered 6 h later than xanthones. At high concentrations of α-mangostin, persister K. pneumoniae cells in the biofilm were about 5 - 10 times more abundant than cells, whereas, with γ-mangostin, they were about 100 times more. CONCLUSION: Two xanthones, α- and γ-mangostin from G. mangostana, induced biofilm formation in K. pneumoniae and promoted persister cells. However, the biofilm formation was reversed by adding 3-methyl-2(5H)-furanone, and even this effect was achieved with gentamicin. In addition, this compound controlled the persister K. pneumoniae cells promoted by α-mangostin. Thus, synthetic, and natural biofilm-inducing compounds could harm human health. Therefore, avoiding these substances and looking for biofilm inhibitors would be a strategy to overcome microbial resistance and recover antibiotics that are no longer used.

Triterpene-enriched fractions from Eucalyptus tereticornis ameliorate metabolic alterations in a mouse model of diet-induced obesity.

ETNOPHARMACOLOGICAL RELEVANCE: Eucalyptus tereticornis Sm. (Eu) is a plant species used in traditional medicine to treat diabetes mellitus. Eu leaf extracts have been shown to regulate immuno-metabolic activities that are associated with obesity and insulin resistance. OBE100 and OBE104 are two natural Eu extracts that are rich in pentacyclic triterpenes. The major compounds identified in OBE100 are ursolic acid (UA), oleanolic acid (OA), and ursolic acid lactone (UAL), and the major compounds identified in OBE104 are UA and OA. AIM OF THE STUDY: This study aimed to investigate the effects of two extracts from Eu leaves with different triterpene composition in a nutritional animal model of prediabetes. METHODS: A mouse model of diet-induced obesity was used to analyze the effects of the OBE100 and OBE104 treatments on metabolic markers and gene expression in liver and visceral adipose tissue. RESULTS: Treating the prediabetic mouse model with OBE100 and OBE104 increased glucose tolerance. However, only the Eu extract that contained three triterpenes reduced mouse body weight, hepatic and adipose fat content, and plasma lipid levels. OBE100 treatment also led to decreased hepatic mRNA levels of PPARA, CPT1A, and SERBP1. In visceral adipose tissue, OBE100 treatment reduced expression of PPARA and ACACA and increased UCP1 expression. CONCLUSIONS: These results suggest that developing a new multitargeting bioactive compound from the natural extract from Eu may help combat obesity and diabetes. Treatment with OBE100 had better effects than OBE104 in a diet-induced obesity mouse model, suggesting that the OBE100 extract, which contains three triterpenes, may be beneficial in combating obesity.

Mode of action of a formulation containing hydrazones and saponins against leishmania spp. Role in mitochondria, proteases and reinfection process.

Toxicity and poor adherence to treatment that favors the generation of resistance in the Leishmania parasites highlight the need to develop better alternatives. Here, we evaluated the in vitro effectiveness of hydrazone derived from chromanes 2-(2,3-dihydro-4H-1-benzothiopyran-4-ylidene) hydrazide (TC1) and 2-(2,3-dihydro-4H-1-benzopyran-4-ylidene) hydrazide (TC2) and the mixture of triterpene saponin hederagenin-3-O-(3,4-O-diacetyl-ß-D-xylopyranosyl-(1à3)-a-L- rhamnopyranosyl-(1à2)-a-L-arabinofuranoside, hederagenin-3-O-(3,4-O-diacetyl-a-L- arabinopyranosyl-(1à3)-a-L-rhamnopyranosyl-(1à2)-a-L-arabinofuranoside and, hederagenin-3-O-(4-O-acetyl-ß-D-xylopyranosyl-(1à3)-a-L-rhamnopyranosyl-(1à2)-a-L-arabinofuranoside from Sapindus saponaria (SS) on L. braziliensis and L. pifanoi. Mixtures of TC1 or TC2 with saponin were formulated for topical application and the therapeutic effectiveness was evaluated in the model for cutaneous leishmaniasis (CL) in golden hamster. The mode of action of these compounds was tested on various parasite processes and ultrastructural parasite modifications. TC1, TC2 and SS showed moderate cytotoxicity when tested independently but toxicity was improved when tested in combination. The compounds were more active against intracellular Leishmania amastigotes. In vivo studies showed that combinations of TC1 or TC2 with SS in 1:1 ratio (w/w) cured 100% of hamsters with no signs associated with toxicity. The compounds did cause changes in the mitochondrial activity of the parasite with a decrease in ATP levels and depolarization of membrane potential and overproduction of reactive oxygen species; nevertheless, these effects were not related to alterations in membrane permeability. The phagolysosome ultrastructure was also affected impacting the survival of Leishmania but the function of the lysosome nor the pH inside the phagolysosome did not change. Lastly, there was a protease inhibition which was directly related to the decrease in the ability of Leishmania to infect and multiply inside the macrophage. The results suggest that the combination of TC1 and TC2 with SS in a 1:1 ratio is capable of curing CL in hamsters. This effect may be due to the ability of these compounds to affect parasite survival and the ability to infect new cells.

Why do we have so many molecules and biodiversity but so few antiparasite medicines? / Porqué tenemos tantas moléculas bioactivas y biodiversidad pero tan pocas medicinas antiparasitarias?

Natural products are isolated from biodiversity, that is, from plants, microorganisms, insects, and marine organisms; most of the biodiversity is found in about 10-12 countries located around the Equator. For a long time, people chose this option to alleviate diseases and the industry to discover new medicines; however, from the 70's onwards synthetic products have displaced them. Today there is a rebirth of natural products research and annually hundreds of new natural and synthetic bioactive molecules are reported in specialized journals. On the other hands, new drugs are continually required and especially there is a deficit of them to treat the so-called Neglected Diseases, which affect and threaten the health of billions of people in the world. These diseases paradoxically affect almost all megadiverse countries. Thus, the richest countries in biodiversity do not benefit from the use of natural products because research, development and production of new medicines are carried out in more technologically advanced countries. Why do we have so many molecules in biodiversity and journals but so few medicines? How could new antiparasite drugs be developed quickly and cheaply in the countries affected by Neglected Diseases? A feasible alternative is the Mining in Press, that is, the search of molecules in scientific literature. In this paper we analyze the reasons why these valuable substances have not become drugs and remain curiosities of laboratories and libraries, and the advantages of using this approach as a source of drugs or templates to other bioactive molecules.

Los productos naturales son aislados de la biodiversidad, es decir, de plantas, microorganismos y organismos marinos; gran parte de la biodiversidad se encuentra en cerca de 10-12 paises localizados alrededor del Ecuador. Por mucho tiempo, la gente ha seleccionado esta opción para aliviar sus enfermedades y la industria para descubrir nuevas medicinas; sin embargo, desde los años 70s los productos sintéticos los han desplazado. Hoy hay un renacimiento de la investigación de productos naturales y anualmente cientos de nuevas moléculas naturales y sintéticas bioactivas son reportados en las publicaciones especializadas. De otro lado, continuamente se requieren nuevas drogas y especialmente hay un déficit de ellas para tratar las llamadas Enfermedades Olvidadas, que afectan y amenazan la salud de miles de millones de personas en el mundo. Estas enfermedades paradójicamente afectan casi todos los países megadiversos. De esta manera, los países más ricos en biodiversidad no se benefician del uso de productos naturales, ya que la investigación, el desarrollo y la producción de nuevas medicinas se lleva a cabo en países tecnológicamente avanzados. Por qué tenemos tantas moléculas en la biodiversidad y en las publicaciones, pero tan pocas medicinas? Cómo podrían las drogas antiparasitarias ser desarrolladas de manera mas rápida y barata en los países afectados por las Enfermedades Olvidadas? Una posible alternativa es la Minería de las Publicaciones, es decir, la búsqueda de moléculas en la literatura científica. En este artículo nosotros analizamos las razones por la cuales esas valiosas sustancias no han llegado a ser drogas y permanecen como curiosidades de los laboratorios y bibliotecas, y las ventajas de usar esta aproximación como una fuente de drogas o modelos de otras moléculas bioactivas.

Biocidal effect of a hexane-soluble extract of Lippia graveolens Kunth (Verbenaceae) / Efecto biocida del extracto hexánico de Lippia graveolens Kunth (Verbenaceae)

Lippia graveolens Kunth (Verbenaceae) is an economically important shrub known in Mexico as Oregano. In this work, the biocidal effect of the hexane extract of L. graveolens leaves was evaluated on two crop pests. Thus, larvae of Spodoptera frugiperda were fed with mixtures of extract and artificial diet. The nematicidal activity was evaluated on juveniles of Meloydogine javanica. Regarding S. frugiperda, quantitative differences between treatments and control were observed in dead pupae, surviving adults, and deformed adults (P < 0.05). All the surviving adults from the extract treatments were deformed. Nematicidal effect was registered, the LC50 and LC90 were 0.672 (0.654-0.690) and 0.965 (0.937-0.998) mg/mL respectively. The extract was characterized by NMR and GC-MS, being thymol the most abundant component (70.6%) in addition to carvacrol (22.8%). The results suggest the consideration of the hexane extract of L. graveolens leaves within the alternatives for the biological control of pests.

Lippia graveolens Kunth (Verbenaceae) es un arbusto con importancia económica conocido en México como Orégano. En éste trabajo se evaluó el efecto biocida del extracto hexánico de hojas L. graveolens sobre dos plagas agrícolas. Así, larvas de S. frugiperda fueron alimentadas con mezclas de dieta artificial y extracto. La actividad nematicida fue evaluada en juveniles de Meloydogine javanica, Respecto a S. frugiperda, se observaron diferencias cuantitativas entre tratamiento y control en cuanto a pupas muertas, adultos sobrevivientes y adultos deformes (P < 0.05). Todos los adultos provenientes de tratamientos con extracto estuvieron malformados. Hubo efecto nematicida, calculándose CL50 y CL90 de 0.672 (0.654-0.690) y 0.965 (0.937-0.998) mg/mL respectivamente. El extracto se caracterizó por RMN y CG-EM. Los compuestos más abundantes fueron timol (70.6%), ademas del carvacrol (22.8%). Los resultados sugieren considerar al extracto hexánico de hojas de L. graveolens dentro de las alternativas para el control biológico de plagas.

In vivo Antimalarial Activity of α-Mangostin and the New Xanthone δ-Mangostin.

Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α-mangostin and a new compound, δ-mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α-Mangostin was more active against the resistant Plasmodium falciparum chloroquine-resistant (FCR3) strain (IC50 = 0.2 ± 0.01 µM) than δ-mangostin (IC50 = 121.2 ± 1.0 µM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances.

Evaluation of the hypoglycemic effects of flavonoids and extracts from Jatropha gossypifolia L.

Jatropha gossypifolia L. (Euphorbiaceae) is a plant widely used in the treatment of type 2 diabetes mellitus (T2DM), but there are few scientific reports validating its activity in this area. In this work and through a bioguided assay, a crude extract stimulated glucose uptake in C2C12 myotubes up to 30%, thereby reducing insulin resistance induced by fatty acids compared to the basal control. A chromatographic fraction applied intraperitoneally (IP) in mice reduced glucose by 42% in a mouse model of T2DM, after administration of 10 doses during 20 days. A flavanone was purified from this active fraction and its structure was assigned by 1H- and 13C-NMR (1D and 2D) and MS. This compound retains the previously reported activity, stimulating in vitro the glucose uptake in a concentration-dependent manner. This study indicates that Jatropha gossypifolia L. extracts enhance glucose uptake in cultured myotubes and adipocytes and also improving glucose tolerance in an in vivo model.

Leishmanicidal and trypanocidal activity of Sapindus saponaria / Actividad leishmanicida y tripanocida de Sapindus saponaria

Leishmaniasis and trypanosomiasis are parasitic diseases with a high infection rate, being a serious public health issue in the new world. Unfortunately, there are few available commercial drugs, poorly efficient and with increasing parasite resistance. Under these condi- tions, there is a need for new molecules to develop new and better drugs. One approach to carry out this search is using traditional medicine as information source to obtain new molecules or extracts to control these parasite diseases. Sapindus saponaria (Sapindaceae) fruit resin is used in Colombia to treat ulcers caused by Leishmaniasis. In a bioguided study, we have analyzed the in vitro effect of fruit resin, chroma- tographical fractions from fruit resin and also pure compounds against Leishmania species (L. panamensis, L. braziliensis, L. amazonensis and L. donovani) and Trypanosoma cruzi. The in vivo antileishmanial effect was established under the hamster model for cutaneous leish- maniasis by L. panamensis; refined extract of S. saponaria and pure saponins displayed high in vitro and in vivo activity as leishmanicides. In addition, extracts caused low viability on T. cruzi amastigotes. The use of the crude extract can be a good alternative against cutaneous leishmaniasis, due to its activity, reduced hemolytic effect, and easy production procedures.

La Leishmaniasis y la tripanosomiasis son enfermedades parasitarias con una alta incidencia, siendo un serio asunto de salud pública en el nuevo mundo. Desafortunadamente, hay pocas drogas comerciales disponibles, con pobre eficiencia y con una creciente resis- tencia parasitaria. Bajo esas condiciones, se necesitan nuevas moléculas para desarrollar nuevas y mejores drogas. Una aproximación para llevar a cabo esa búsqueda es usar la medicina tradicional como fuente de información para obtener nuevas moléculas o extractos para con- trolar esas enfermedades parasitarias. La resina de Sapindus saponaria (Sapindaceae) se usa en Colombia para tratar úlceras causadas por la Leishmaniasis. En un estudio bioguiado, se analizó el efecto in vitro de varios extractos de la resina, sus fracciones cromatográficas y algu- nos compuestos puros, contra varias especies de Leishmania (L. panamensis, L. braziliensis, L. amazonensis y L. donovani) panamensis y Trypanosoma cruzi. El efecto lesihmanicida in vivo fue establecido usando el modelo en hamster de leishmaniasis cutánea producida por L. panamensis; los extractos refinados de S. saponaria y las saponinas puras mostraron alta actividad in vitro e in vivo como leishmanicidas. Además, los extractos causaron una baja viabilidad en amastigotes de T. cruzi. El uso de extractos refinados en vez de saponinas puras podría ser una buena alternativa contra leishmaniasis cutánea debido a su actividad, poco efecto hemolítico y procedimientos de producción mucho más fáciles.

Effect of salicylic acid and structurally related compounds in the accumulation of phytoalexins in cotyledons of common bean (Phaseolus vulgaris L.) cultivars.

In the present work, isoflavonoid phytoalexin production in response to the application of salicylic acid in cotyledons of four common bean (Phaseolus vulgaris) cultivars (SA) was evaluated. The time-course and dose-response profiles of the induction process were established by quantifying the isoflavonoids by HPLC. Cotyledons of anthracnose-resistant cultivars induced by SA produced substantially higher phytoalexin contents as compared to the susceptible ones. In addition, maximum levels of phytoalexins (50-100 fold increases) were reached between 96 and 144 h, and when a concentration of SA from 3.62 to 14.50 mM was used. The observations also indicate that there was a relatively good correlation between the phytoalexin contents and the inhibitory effect against C. lindemuthianum; the higher antifungal activity was observed during the first 48 hours for extracts from cotyledons treated with SA at 1.45 and 3.62 mM, and between 96 and 144 h after induction. Finally, compounds structurally related to SA (dihydro-quinazolinones and some imines) showed a strong elicitor effect. Moreover, induced extracts from cotyledons treated with these potential elicitors, besides the properly elicitors, displayed a weak to moderated antifungal activity. These compounds may be considered good candidates for developing of new phytoprotectants. Furthermore, phytoalexin-eliciting substances may contribute for selecting disease resistant cultivars.

Diosgenone synthesis, anti-malarial activity and QSAR of analogues of this natural product.

Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 µM vs. 10.1 µM, 2.9 µM and 11.3 µM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.

Actividad tripanocida y citotóxica de extractos de plantas colombianas / Trypanocidal and cytotoxic activity of extracts of Colombian plants

Introducción. El tratamiento de la enfermedad de Chagas está basado en sólo dos medicamentos de eficacia limitada y con importantes efectos colaterales. La gran biodiversidad de la flora colombiana hace de la bioprospección una alternativa potencial en la búsqueda de nuevos antiparasitarios. Objetivo. Evaluar in vitro el potencial tripanocida y la citotoxicidad de extractos obtenidos de 23 plantas colombianas. Materiales y métodos. Se obtuvieron extractos de hojas, de tallos o de la planta entera, en solventes de diferente polaridad. La actividad contra epimastigotes y la citotoxicidad se evaluaron por el micrométodo enzimático con MTT. Los extractos activos contra epimastigotes y con baja citotoxicidad se evaluaron también en tripomastigotes y amastigotes intracelulares. Resultados. Se reporta la actividad tripanocida de 13 plantas colombianas y se confirma el efecto biológico de cuatro especies previamente evaluadas. Cuatro extractos activos en epimastigotes también fueron activos en tripomastigotes y, uno de ellos, en amastigotes. Este extracto fue aislado de la planta Hieronyma antioquensis, y presentó CI50 de 3,125, 11,48 y 2,85 µg/ml, e índices de selectividad de 25,7 y 27, para epimastigotes, tripomastigotes y amastigotes, respectivamente. Los resultados sugieren que este extracto es un candidato promisorio para el tratamiento de la enfermedad de Chagas. Conclusión. La flora colombiana es una fuente potencial de nuevas sustancias para la quimioterapia contra la enfermedad de Chagas. El micrométodo enzimático con MTT es una herramienta útil para la tamización de la actividad biológica en epimastigotes y posterior selección para ensayos con otros estadios del parásito.

Introduction. The treatment of Chagas disease is based on only two drugs with limited efficacy and significant side effects. The rich biodiversity of the Colombian flora makes bio-prospecting a potential alternative in the search for new antiparasitic drugs. Objective. Potential trypanocidal activity and cytotoxicity was assessed in extracts from 23 Colombian plants. Materials and methods. Extracts of leaves, stems, or of the whole plants were obtained in solvents of a range of polarities. The activity against Trypanosoma cruzi epimastigotes and the cytotoxicity were evaluated by the MTT enzymatic micro-method. Extracts active against epimastigotes and with lowcytotoxicity were also tested on trypomastigotes and intracellular amastigotes. Results. Among the extracts, biological activity was confirmed in 4 species. The extracts were active on epimastigotes and trypomastigotes; one was active also against amastigotes. The latter extract was isolated from the plant Hieronyma antioquensis and presented IC50 of 3.1 mg/ml for epimastigotes, 11.5mg/ml for trypomastigotes and 2.9 mg/ml for amastigotes. The selectivity indexes were 25, 7, and 27 respectively. Conclusions. The extract from H. antioquensis proved a promising candidate for Chagas disease treatment. Futhermore, the MTT enzymatic micromethod was a useful tool for screening biological activity on epimastigotes and other stages of the parasite for further extract trials.

New promising Euphorbiaceae extracts with activity in human lymphocytes from primary cell cultures.

CONTEXT: Euphorbiaceae plants exhibit anti-inflammatory and immunomodulatory properties. METHODS: We evaluated the activity of 14 extracts from seven Euphorbiaceae plants on primary immune cell cultures from healthy individuals. Peripheral blood mononuclear cells (PBMC) were exposed to the extracts w/o phytohaemagglutinin A or cycloheximide as agents that induce proliferation or apoptosis in PBMC, respectively. RESULTS: We found that five up to 14 Euphorbiaceae's extracts had the ability to modulate at least one of the immune parameters evaluated in this study. However, only the latex extracts of Euphorbia cotinifolia and Euphorbia tirucalli strongly induced both proliferation and apoptosis in PBMC. These extracts were further subfractioned by silica gel column chromatography. Two subfractions with enhanced activity in comparison to the crude extracts were obtained. Although these subfractions induced proliferation on both CD3(+) and CD3(-) cells, the most prominent effects were observed in the former subpopulation. Interestingly, the subfraction from E. tirucalli induced lymphocyte proliferation without the need of accessory cells; this ability was not inhibited by the carbohydrates d-galactose and α-Methyl-D-Mannopyranoside. CONCLUSIONS: Altogether, these results reveal the presence of novel candidates within the Euphorbia plants to induce proliferation and apoptosis in human lymphocytes, mainly in CD3(+) T cells.

[Trypanocidal and cytotoxic activity of extracts of Colombian plants]. / Actividad tripanocida y citotóxica de extractos de plantas colombianas.

INTRODUCTION: The treatment of Chagas disease is based on only two drugs with limited efficacy and significant side effects. The rich biodiversity of the Colombian flora makes bio-prospecting a potential alternative in the search for new antiparasitic drugs. OBJECTIVE: Potential trypanocidal activity and cytotoxicity was assessed in extracts from 23 Colombian plants. MATERIALS AND METHODS: Extracts of leaves, stems, or of the whole plants were obtained in solvents of a range of polarities. The activity against Trypanosoma cruzi epimastigotes and the cytotoxicity were evaluated by the MTT enzymatic micro-method. Extracts active against epimastigotes and with low cytotoxicity were also tested on trypomastigotes and intracellular amastigotes. RESULTS: Among the extracts, biological activity was confirmed in 4 species. The extracts were active on epimastigotes and trypomastigotes; one was active also against amastigotes. The latter extract was isolated from the plant Hieronyma antioquensis and presented IC(50) of 3.1 mg/ml for epimastigotes, 11.5 mg/ml for trypomastigotes and 2.9 mg/ml for amastigotes. The selectivity indexes were 25, 7, and 27 respectively. CONCLUSIONS: The extract from H. antioquensis proved a promising candidate for Chagas disease treatment. Futhermore, the MTT enzymatic micromethod was a useful tool for screening biological activity on epimastigotes and other stages of the parasite for further extract trials.

Effects of diterpenes from latex of Euphorbia lactea and Euphorbia laurifolia on human immunodeficiency virus type 1 reactivation.

The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication in patients treated with highly active antiretroviral therapy, referred to as HAART. HIV-1 reservoirs are long-lived resting CD4+ memory cells containing the virus latently integrated. Since the HIV-1 reservoirs are not targeted by HAART, reactivation therapy has been suggested to purge viral latency. Bioassay-guided study of an ethyl acetate extract of Euphorbia laurifolia afforded two isomeric diterpenes that showed differential activity over HIV-1 reactivation. A previously reported compound was isolated too from Euphorbia lactea. This compound showed a potent HIV-1 reactivating effect. Bioassays results showed that HIV-1 reactivation activity is influenced by distinct structural characteristics.

Phenalenone-type compounds from Musa acuminata var. "Yangambi km 5" (AAA) and their activity against Mycosphaerella fijiensis.

Two perinaphthenone-type compounds (1 and 2) were isolated together with four known phenylphenalenones (3-6) from the rhizomes of Musa acuminata var. "Yangambi km 5". The structures of the new phenalenones were assigned as 2-hydroxy-1H-phenalen-1-one (1) and 2-methoxy-1H-phenalen-1-one (2) on the basis of their spectroscopic data and were confirmed by synthesis. Compounds 1 and 2 displayed significantly enhanced activity against Mycosphaerella fijiensis in comparison with other phenylphenalenones.

Leishmanicidal activity of Pycnoporus sanguineus.

In the search for antiparasite compounds from the Colombian flora, an active compound against Leishmania (Viannia) panamensis amastigotes was isolated from the fungi Pycnoporus sanguineus. The structural elucid-ation was achieved with spectroscopic methods ((1)H and (13)C NMR and MS). This compound was identified as ergosterol 5,8-endoperoxide.