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L L Leon

Publications and source records attributed to L L Leon.

At least 19 recordsLinked to original sources
PubMed2006

Antileishmanial activity of indole alkaloids from Aspidosperma ramiflorum.

The present study was designated to evaluate the antileishmanial activity of acid and basic fractions that were obtained after acid-basic extraction, from ethanolic 70% crude extract and pure compounds from the stem bark of Aspidosperma ramiflorum. The basic alkaloidal fraction presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis (LD(50) value<47 microg/ml). Based on these findings, the basic fraction was fractionated on silica gel column chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 16.3+/-1.6 microg/ml and 4.9+/-0.9 microg/ml, respectively). Our results are promising, showing that these compounds are biologically active against Gram-positive bacteria.

Animals↗
PubMed2005

Amidine derivatives and Leishmania amazonensis: an evaluation of the effect of nitric oxide (NO) production on the parasite-macrophage interaction.

Previous work has demonstrated that N-N'-diphenyl-R-benzamidine was highly effective against Leishmania amazonensis promastigotes/axenic amastigotes and Trypanosoma evansi trypomastigotes and the compound with a methoxy substituent, was the most effective derivative in the parasite-macrophage interaction. Comparative analysis of the nitric oxide (NO) released from the culture infection's supernatant showed the amidine to be less effective than pentamidine Isethionate as a reference drug. Additionally, in order to verify if the methoxylated derivative interferes with NO production by L. amazonensis, the effect of the amidine on the constitutive nitric oxide synthase (cNOS) purified from parasites, was examined, but demonstrated less activity in comparison with the reference drug. This data contributes to studies concerning the metabolic targets present in Leishmania parasites for leishmanicidal drugs.

Amidines↗
PubMed2004

2-propen-1-amine derivatives and their synthetic intermediates: activity against pathogenic trypanosomatids.

The potential activity of three new derivatives of 3-(4'-Y-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine (2-PAMs) was assayed against Trypanosoma cruzi and Leishmania amazonensis. They showed higher activity against trypomastigotes and epimastigotes of T. cruzi than the standard drugs, crystal violet and nifurtimox. Besides these derivatives, a series of eleven 2-PAMs derivatives and the corresponding intermediates, biphenyl methanones (BPMs) were assayed against promastigotes of L. amazonensis, showing that the 2-PAMs were remarkably more active than the BPMs. The PAMs 2c, 2e and 2j were about 2-fold more active that pentamidine isothionate and between 27.2- and 46.4-fold less toxic to V79 mammalian cells. The present results encourage further studies, especially against intracellular parasites and in experimental animals.

Animals↗
PubMed2003

Cyclic 3'-5' guanosine monophosphate-dependent activity in Leishmania amazonensis.

Although there are some data concerning the nitric oxide and the cyclic 3'-5'guanosine monophosphate (cGMP) signaling pathway in trypanosomatids, there is no report about the cGMP-dependent enzymatic activity identification. In this sense, a cGMP dependent activity was detected on soluble fraction from Leishmania amazonensis promastigotes with a high metacyclic level. This information is valuable in order to explore the metabolic pathway of G kinase protein in this parasite.

Animals↗
PubMed2001

Protein kinase A of Leishmania amazonensis as a potential target for methoxy-amidine.

Cyclic 3',5'-adenosine monophosphate (cAMP) is one of the most important signaling molecules for cell growth and differentiation in several systems including protozoal parasites such as Trypanosoma cruzi and Leishmania species. The most important event during Leishmania developmental cycle is the differentiation of procyclic into metacyclic promastigotes, which is associated with the appearance of pathogenicity. As previously demonstrated Leishmania amazonensis metacyclogenesis is associated with an increase of a protein kinase A activity, and therefore further studies on the activity of this phosphorylating enzyme as a target for chemotherapy were performed. Among several amidine derivatives tested by the authors against trypanosomatids (T. cruzi, T. evansi and L. amazonensis) the most effective compounds was defined as that with a methoxy group as substituent. In this work the inhibitory effect of this derivative on the phosphorylating activity of cAMP-dependent protein kinase (PKA) of promastigotes (containing high amounts of metacyclic forms) and axenic amastigotes of L. amazonensis is demonstrated. Soluble fractions (SF) and enriched membrane fractions (MF) were submitted to anion exchange chromatography in a DEAE-cellulose column and the collected fractions used to evaluate the phosphorylating activity associated with cAMP, in the presence/absence of methoxy-amidine and pentamidine (CAS 100-33-4), the latter being used as reference drug.

Adenylyl Cyclases↗
PubMed2001

Biological activities of Curcuma longa L.

There are several data in the literature indicating a great variety of pharmacological activities of Curcuma longa L. (Zingiberaceae), which exhibit anti-inflammatory, anti-human immunodeficiency virus, anti-bacteria, antioxidant effects and nematocidal activities. Curcumin is a major component in Curcuma longa L., being responsible for its biological actions. Other extracts of this plant has been showing potency too. In vitro, curcumin exhibits anti-parasitic, antispasmodic, anti-inflammatory and gastrointestinal effects; and also inhibits carcinogenesis and cancer growth. In vivo, there are experiments showing the anti-parasitic, anti-inflammatory potency of curcumin and extracts of C. longa L. by parenteral and oral application in animal models. In this present work we make an overview of the pharmacological activities of C. longa L., showing its importance.

Animals↗
PubMed1999

Amidine derivatives are highly effective against Trypanosoma evansi trypomastigotes.

The in vitro effect of N,N'-diphenyl-4-R-benzamidine (where R = H, CN, Br, Cl, CH3, OCH3 and NO2) in three isolates of Trypanosoma evansi was studied. The compounds were solubilized in dimethysulphoxide (DMSO) and tested in a concentration range of 5 to 160 micrograms/ml. The parasites were isolated from a horse, a dog and a coati. They were maintained in immunosuppressed rats, since they could not be cultured in vitro, and further purified through a diethylaminoethanol (DEAE) column. The trypomastigotes obtained were mixed with different concentrations of the drugs and after incubation at 26 degrees C for 24 h, the remaining parasites were counted in a Neubauer chamber. The percentage of inhibition was evaluated compared with the control, without the drugs. Most of the amidine derivatives showed high activity against the three T. evansi isolates, but different patterns of sensitivity to the tested compounds were observed. At least four compounds with Br, Cl, OCH3 and NO2 as substituents, were much more effective than Berenil [4,4'-(diazoamine)-dibenzamidine aceturate], the reference drug used, which is included in the same chemical class of amidines.

Animals↗
PubMed1998

Leishmania amazonensis: long-term cultivation of axenic amastigotes is associated to metacyclogenesis of promastigotes.

Axenic Leishmania amazonensis cultures were obtained (with 2 years of follow-up) in Schneider's medium at pH 5.5 and a temperature of 32 degrees C. Differentiation of promastigotes into amastigotes is directly associated with the metacyclogenesis rate of the original promastigotes. Promastigote cultures containing different percentages of metacyclic forms, as evaluated by the complement lysis test, resulted in axenic amastigote cultures containing a variable amount of undifferentiated forms. We observed that a culture originally containing a large amount of metacyclic forms (73%) underwent a complete differentiation process, resulting in a 100% amastigote culture with no promastigote forms. All other cultures (with a decreasing amount of metacyclic forms: 50% and fewer) failed to differentiate completely, resulting in cultures with increasing percentages of promastigote contamination. The amastigote/promastigote rate in these cultures has been maintained at the same level thus far. The axenic Leishmania amazonensis amastigotes were cryopreserved, thawed as such, and successfully cultivated under appropriately defined growth conditions.

Animals↗
PubMed1997

The potential effects of new synthetic drugs against Leishmania amazonensis and Trypanosoma cruzi.

Amidine derivatives, never used before on trypanosomatids, were tested against Leishmania amazonensis and Trypanosoma cruzi. These drugs in doses up to 500 mg/kg inoculated into Swiss mice did not show any toxic effect (Santos, 1993). The in vitro effect of N,N'-diphenyl-4-R- benzamidine was evaluated. L. amazonensis promastigotes, epimastigotes and blood forms of T. cruzi, were assayed with/without the drugs in axenic media, using pentamidine isethionate and benznidazole, as reference drugs. The results were very promising for L. amazonensis, showing that the most active compounds were the metoxy and Br-derivatives, with LD50 of 20 microM and 22 microM, respectively. In general the amidines showed lower activity against T. cruzi than L. amazonensis. The most active compounds against blood trypomastigotes were the same metoxy and Br-derivatives, but in much higher concentrations, e.g. as LD50 of 59 nM and 251 nM, respectively. All amidines had a very low activity against epimastigotes, and the only active compounds were the halogen-derivatives with LD50 = 424 nM for the Br-derivative and LD50 of 474 nM for the C1-derivative.

Animals↗
PubMed1994

Proteinase activities during temperature-induced stage differentiation of species complexes of Leishmania.

We have examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), using gelatin, bovine serum albumin (BSA) or human IgG as substrate, proteinase activities in cell lysates from selected species complexes of Leishmania. The inhibition of proteinase activity caused by the reagent L-trans-epoxysuccinylleucylamido(4-guanidino)butane (E-64), which is known to act only on cysteinyl proteinases, revealed a 31 kDa component of this class of enzymes in soluble, but not in membrane-enriched preparations, of either L. amazonensis or L. major-like parasites from the New World. The proteinase component was detectable in the leishmanial multiplicative promastigote stage (log phase) and its concentration apparently increased during the thermally induced transformation of promastigotes to amastigote-like forms in vitro. Comparative studies revealed that taxonomically distinct species complexes of Leishmania possess high amastigote cysteine proteinase activity. This feature, however, was lacking in other developmental stages of the species (L. braziliensis, L. chagasi, L. aethiopica, and L. donovani) analyzed. Furthermore, lesion amastigotes of L. amazonensis displayed ultrastructurally recognizable megasomes, but megasome-like or large multivesicular body organelles could be detected only in axenic amastigotes of both L. amazonensis and L. major-like species.

Animals↗
PubMed1986

Comparative studies of Leishmania soluble antigens by crossed-immunoelectrophoresis: demonstration of specific antigens to L. mexicana and L. braziliensis.

The antigenic relationship between two species of Leishmania (L. mexicana amazonensis and L. braziliensis braziliensis) was analysed using crossed-immunoelectrophoresis with an intermediate gel. Rabbit hyperimmune sera were prepared by subcutaneous inoculations of soluble antigens obtained from each species, emulsified in Freund's adjuvant. The antisera were then tested by immunodiffusion and electrophoresis; soluble antigens obtained from promastigote forms were submitted to ultrasonication and ultracentrifugation. Immunoelectrophoresis with homologous and heterologous antisera demonstrated the existence of some antigens which were species specific and some which were common to both species. The importance of these antigens is discussed.

Animals↗
PubMed1982

Induction of the acute-phase protein serum amyloid P in experimental Chagas' disease.

Serum amyloid P protein (SAP), which shares several structural properties with C-reactive protein, has been recently identified as an acute-phase reactant in mice. In this study, the systemic inflammatory response of mice to infection with Trypanosoma cruzi was characterized with respect to induction of SAP as well as to stage-specific alterations on complement C3 and C4 levels. The SAP response depended on the dose and infectivity of the parasites. Kinetic data indicated a close temporal relationship between the onset of parasitemia and induction of SAP. The levels of SAP were maximally enhanced (1,050%) by the time parasitemia started to regress, and the response remained elevated as the infection entered the latency phase. The decline in parasitemia was paralleled by a significant reduction in C3 levels. A reciprocal relationship between the extent of parasitemia and SAP/C3 levels became apparent when these parameters were compared in individual inbred mice during the time of decreasing parasitemia.

Amyloid↗
PubMed1980

Immunization of mice with Trypanosoma cruzi polyribosomes.

Studies were carried out with a polyribosomal fraction isolated from Trypanosoma cruzi Y epimastigotes, with the intention to determine both its immunogenic activity and the degree of protection it could induce against experimental T. cruzi infection. This fraction was assayed in four groups of mice by using different schedules of vaccination and varying the dose, intervals, and route of administration. Seven days after the last dose, the animals were sacrificed for immunological studies or subjected to challenge with T. cruzi trypomastigotes. The results obtained in all schedules showed that our polyribosomal fraction only induced a weak antibody response, but was capable of evoking an expressive cellular response. It was also shown that this fraction has the capacity of inducing a high degree of protection against T. cruzi infection, as determined by the decrease of parasitemia and the prolonged survival time of immunized animals.

Animals↗