scholarly journals Selective Effect of 2′,6′-Dihydroxy-4′-Methoxychalcone Isolated from Piper aduncum on Leishmania amazonensis

1999 ◽  
Vol 43 (5) ◽  
pp. 1234-1241 ◽  
Author(s):  
Eduardo Caio Torres-Santos ◽  
Davyson Lima Moreira ◽  
Maria Auxiliadora C. Kaplan ◽  
Maria Nazareth Meirelles ◽  
Bartira Rossi-Bergmann
Keyword(s):  
Simple Structure ◽  
Fluorescein Isothiocyanate ◽  
Inhibitory Effect ◽  
Leishmania Amazonensis ◽  
Significant Activity ◽  
Ultrastructural Studies ◽  
Intracellular Amastigotes ◽  
Effective Doses ◽  
Piper Aduncum

ABSTRACT 2′,6′-Dihydroxy-4′-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 μg/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 μg/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 μg of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.

scholarly journals Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Angela Maria Arenas Velásquez ◽  
Willian Campos Ribeiro ◽  
Vutey Venn ◽  
Silvia Castelli ◽  
Mariana Santoro de Camargo ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Parasite Load ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
Leishmania Amazonensis ◽  
Content Type ◽  
Intracellular Amastigotes ◽  
Therapeutic Alternatives

ABSTRACT Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. We report here the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N′-dimethylbenzylamine (Hdmba) against Leishmania amazonensis. The compound [Pd(dmba)(μ-N3)]2 (CP2) inhibits promastigote growth (50% inhibitory concentration [IC50] = 13.2 ± 0.7 μM) and decreases the proliferation of intracellular amastigotes in in vitro incubated macrophages (IC50 = 10.2 ± 2.2 μM) without a cytotoxic effect when tested against peritoneal macrophages (50% cytotoxic concentration = 506.0 ± 10.7 μM). In addition, CP2 was also active against T. cruzi intracellular amastigotes (IC50 = 2.3 ± 0.5 μM, selective index = 225), an indication of its potential for use in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c showed an 80% reduction in parasite load compared to infected and nontreated animals. Also, compared to amphotericin B treatment, CP2 did not show any side effects, which was corroborated by the analysis of plasma levels of different hepatic and renal biomarkers. Furthermore, CP2 was able to inhibit Leishmania donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this parasite. (This study has been registered at ClinicalTrials.gov under identifier NCT02169141.)

Effect of Isolated Proteins from Crotalus Durissus Terrificus Venom on Leishmania (Leishmania) Amazonensis-Infected Macrophages

2020 ◽  
Vol 27 (8) ◽  
pp. 718-724 ◽  
Author(s):  
Simone Katz ◽  
Clara Lúcia Barbiéri ◽  
Fernanda Paula Martins Soler ◽  
Andreimar Martins Soares ◽  
Maria Cristina Chavantes ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Inhibitory Effect ◽  
Leishmania Amazonensis ◽  
Significant Activity ◽  
Crotalus Durissus Terrificus ◽  
Mucocutaneous Leishmaniasis ◽  
Potential Alternative ◽  
Etiological Agents ◽  
Crotalus Durissus

Background: Cutaneous and mucocutaneous leishmaniasis are parasitic diseases characterized by skin manifestations. In Brazil, Leishmania (Leishmania) amazonensis is one of the etiological agents of cutaneous leishmaniasis. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, as they are often highly toxic, poorly tolerated and of variable effectiveness. This study aimed to evaluate in vitro the leishmanicidal activity of toxins isolated from Crotalus durissus terrificus venom as a new approach for the treatment of leishmaniasis. Methods: The comparative effects of crotamine, crotoxin, gyrotoxin, convulxin and PLA2 on bone marrow-derived macrophages infected with L. (L.) amazonensis as well as the release of TGF-β from the treated macrophages were studied. Results and Discussion: Crotamine had the strongest inhibitory effect on parasite growth rate (IC50: 25.65±0.52 μg/mL), while convulxin showed the weakest inhibitory effect (IC50: 52.7±2.21 μg/mL). In addition, TGF-β was significantly reduced after the treatment with all toxins evaluated. Conclusion: The Crotalus durissus terrificus toxins used in this study displayed significant activity against L. (L.) amazonensis, indicating that all of them could be a potential alternative for the treatment of cutaneous leishmaniasis.

Inversion in Volvox tertius: the effects of con A

1981 ◽  
Vol 48 (1) ◽  
pp. 355-366
Author(s):  
G.W. Ireland ◽  
S.E. Hawkins
Keyword(s):  
Cell Division ◽  
Cell Shape ◽  
Shape Change ◽  
Fluorescein Isothiocyanate ◽  
Inhibitory Effect ◽  
Con A ◽  
Cell Shape Change ◽  
Enhanced Production ◽  
Inside Out

During the development of Volvox tertius spheroids, a single-celled gonidium enlarges and undergoes multiple incomplete cleavages to give an embryo which is ‘inside-out’ with respect to the adult organism. A morphogenetic movement, termed ‘inversion’, turns this hollow ball of cells ‘inside-out’ through a hole, the phialopore. In V. tertius this phialopore possesses 4 inwardly directed lips. Normal inversion was studied in vitro in slide chambers and involved cell-shape changes accompanied by the production of pseudopodia and the bending backwards of the phialopore lips. 100 micrograms/ml Con A specifically and reversibly blocked inversion. Despite the inhibitory effect on cell division, the blocking of inversion was not due to the blocking of the last cell division some 50–100 min prior to inversion. Neither did the first cell-shape change from pear- to spindle-shape appear blocked. A feature of inhibition by Con A was the enhanced production of pseudopodia by embryos blocked at inversion, and the abnormal production of pseudopodia by embryos blocked at earlier stages. Non-inverting embryos showed internal flagella. We suggest that the Con A block to inversion, which may be reversed by alpha-methyl mannoside, arises from the prevention of backwards-bending of the phialopore lips. Fluorescein-isothiocyanate-Con A bound to embryo and cell coat, ane more strongly to the embryo at pre-inversion. SDS-polyacrylamide gel analysis of proteins isolated from embryos showed 4 glycoprotein bands, but Con A binding to these bands could not be demonstrated.

scholarly journals Improvement of In Vitro and In Vivo Antileishmanial Activities of 2′,6′-Dihydroxy-4′-Methoxychalcone by Entrapment in Poly(d,l-Lactide) Nanoparticles

1999 ◽  
Vol 43 (7) ◽  
pp. 1776-1778 ◽  
Author(s):  
Eduardo Caio Torres-Santos ◽  
José M. Rodrigues ◽  
Davyson L. Moreira ◽  
Maria Auxiliadora C. Kaplan ◽  
Bartira Rossi-Bergmann
Keyword(s):  
Polymeric Nanoparticles ◽  
Leishmania Amazonensis ◽  
Antileishmanial Activity ◽  
Antileishmanial Activities ◽  
Piper Aduncum

ABSTRACT The inhibition of intracellular Leishmania amazonensisgrowth by 2′,6′-dihydroxy-4′-methoxychalcone (DMC) isolated fromPiper aduncum was further enhanced after encapsulation of DMC in polymeric nanoparticles. Encapsulated DMC also showed increased antileishmanial activity in infected BALB/c mice, as evidenced by significantly smaller lesions and fewer parasites in the lesions.

scholarly journals Role of Key Micronutrients from Nutrigenetic and Nutrigenomic Perspectives in Cancer Prevention

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 283 ◽  
Author(s):  
Alexandra Irimie ◽  
Cornelia Braicu ◽  
Sergiu Pasca ◽  
Lorand Magdo ◽  
Diana Gulei ◽  
...  
Keyword(s):  
Scientific Literature ◽  
Inhibitory Effect ◽  
General View ◽  
Molecular Alteration ◽  
Gene Level ◽  
Effective Doses ◽  
Cancer Inhibition

Regarding cancer as a genetic multi-factorial disease, a number of aspects need to be investigated and analyzed in terms of cancer’s predisposition, development and prognosis. One of these multi-dimensional factors, which has gained increased attention in the oncological field due to its unelucidated role in risk assessment for cancer, is diet. Moreover, as studies advance, a clearer connection between diet and the molecular alteration of patients is becoming identifiable and quantifiable, thereby replacing the old general view associating specific phenotypical changes with the differential intake of nutrients. Respectively, there are two major fields concentrated on the interrelation between genome and diet: nutrigenetics and nutrigenomics. Nutrigenetics studies the effects of nutrition at the gene level, whereas nutrigenomics studies the effect of nutrients on genome and transcriptome patterns. By precisely evaluating the interaction between the genomic profile of patients and their nutrient intake, it is possible to envision a concept of personalized medicine encompassing nutrition and health care. The list of nutrients that could have an inhibitory effect on cancer development is quite extensive, with evidence in the scientific literature. The administration of these nutrients showed significant results in vitro and in vivo regarding cancer inhibition, although more studies regarding administration in effective doses in actual patients need to be done.

scholarly journals Fluorescence studies on modes of cytochalasin B and phallotoxin action on cytoplasmic streaming in Chara.

1981 ◽  
Vol 88 (2) ◽  
pp. 364-372 ◽  
Author(s):  
E A Nothnagel ◽  
L S Barak ◽  
J W Sanger ◽  
W W Webb
Keyword(s):  
Cytoplasmic Streaming ◽  
Cytochalasin B ◽  
Fluorescein Isothiocyanate ◽  
Inhibitory Effect ◽  
Actin Binding ◽  
Actin Bundles ◽  
Fluorescence Studies ◽  
Direct Contrast ◽  
Fibroblastic Cells

Various investigations have suggested that cytoplasmic streaming in characean algae is driven by interaction between subcortical actin bundles and endoplasmic myosin. To further test this hypothesis, we have perfused cytotoxic actin-binding drugs and fluorescent actin labels into the cytoplasm of streaming Chara cells. Confirming earlier work, we find that cytochalasin B (CB) reversibly inhibits streaming. In direct contrast to earlier investigators, who have found phalloidin to be a potent inhibitor of movement in amoeba, slime mold, and fibroblastic cells, we find that phalloidin does not inhibit streaming in Chara but does modify the inhibitory effect of CB. Use of two fluorescent actin probes, fluorescein, isothiocyanate-heavy meromyosin (FITC-HMM) and nitrobenzoxadiazole-phallacidin (NBD-Ph), has permitted visualization of the effects of CB and phalloidin on the actin bundles. FITC-HMM labeling in perfused but nonstreaming cells has revealed a previously unobserved alteration of the actin bundles by CB. Phalloidin alone does not perceptibly alter the actin bundles but does block the alteration by CB if applied as a pretreatment, NBD-Ph perfused into the cytoplasm of streaming cells stains actin bundles without inhibiting streaming. NBD-Ph staining of actin bundles is not initially observed in cells inhibited by CB but does appear simultaneously with the recovery of streaming as CB leaks from the cells. The observations reported here are consistent with the established effects of phallotoxins and CB on actin in vitro and support the hypothesis that streaming is generated by actin-myosin interactions.

scholarly journals Effect of Potentilla Fulgens L. on Selected Enzyme Activities and Altered Tissue Morphology in Diabetic Mice

2018 ◽  
Vol 35 (03) ◽  
pp. 153-160 ◽  
Author(s):  
Suktilang Majaw ◽  
Sooni Challam ◽  
Donkupar Syiem
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Eye Lens ◽  
Diabetic Mice ◽  
Ultrastructural Alteration ◽  
Ultrastructural Studies ◽  
Transmission Electron ◽  
Eye Tissues ◽  
Insight Into

Introduction The objective of the present study was to investigate the in vitro inhibitory effect of the Potentilla fulgens extract on amylase, α- and β-glucosidase, and lipase, as well as its effect on the ultrastructure of the liver, of the kidneys, and of the eye tissues in alloxan-induced diabetic mice. The present study was designed to get further insight regarding the action of P. fulgens from what has been previously known and reported about this plant. Materials and Methods Roots of P. fulgens were extracted with 10 volumes of aqueous-methanol solution (1:4), and the prepared extract was used for in vitro inhibitory activity on amylase, α-glucosidase, β-glucosidase, and lipase. Afterwards, the plant extract was intraperitoneally administered for alternated days (250 mg/kg body weight) to diabetic mice for 4 weeks, and an ultrastructural examination of the liver, the kidneys and the eye tissues was performed using a transmission electron microscope (JEM-100 CX II, Jeol Ltd., Tokyo Japan). Results The P. fulgens extract showed inhibitory activity against all the four enzymes (amylase, α- and β-glucosidase, and lipase), with the highest percentage of inhibition (94.57% ± 0.16 at 1 mg/mL) being observed against α-glucosidase when compared with the standard. The ultrastructural studies revealed a distortion in the structure of the nuclei and of the mitochondria in the kidneys and liver tissues of diabetic mice. Distortion of cell shape and disturbed orientation was observed in the eye lens of diabetic mice. The P. fulgens extract reversed/protected/reduced the ultrastructural alteration observed in the tissues (liver, kidney, and eye lens) of diabetic mice. Conclusion The inhibitory effect of the P. fulgens extract against the aforementioned enzymes and its protective effect on the tissues of diabetic mice against alloxan-induced diabetes add further insight into the antidiabetic properties of this plant.

scholarly journals Growth-Inhibitory Effect of Heparin on Babesia Parasites

2004 ◽  
Vol 48 (1) ◽  
pp. 236-241 ◽  
Author(s):  
Sabine Bork ◽  
Naoaki Yokoyama ◽  
Yuzuru Ikehara ◽  
Sanjay Kumar ◽  
Chihiro Sugimoto ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Fluorescein Isothiocyanate ◽  
Inhibitory Effect ◽  
Laser Scanning Microscopy ◽  
Babesia Bovis ◽  
Confocal Laser ◽  
Intracellular Parasites ◽  
Low Concentrations

ABSTRACT We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes.

Design, Synthesis and Antileishmanial Activity of Naphthotriazolyl-4- Oxoquinolines

2018 ◽  
Vol 18 (17) ◽  
pp. 1454-1464 ◽  
Author(s):  
Vanessa G. Oliveira ◽  
Viviane dos Santos Faiões ◽  
Gabrieli B.R. Gonçalves ◽  
Miriam F.O. Lima ◽  
Fernanda C.S. Boechat ◽  
...  
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Cycloaddition Reaction ◽  
Public Health Problem ◽  
Leishmania Amazonensis ◽  
Antileishmanial Activity ◽  
Design Synthesis ◽  
Intracellular Amastigotes ◽  
Ic50 Values ◽  
Therapeutic Alternatives

Background: Leishmaniasis is a neglected public health problem caused by several protozoanspecies of the genus Leishmania. The therapeutic arsenal for treating leishmaniasis is quite limited, raising concerns about the occurrence of resistant strains. Furthermore, most of these drugs were developed more than 70 years ago and suffer from poor efficacy and safety and are not well adapted to the needs of patients. Therefore, research on novel natural or synthetic compounds with antiparasitic activity is urgently needed. In this paper, we evaluated the effect and the mechanism of action of naphthotriazolyl-4-oxoquinolines on promastigotes and intracellular amastigotes of Leishmania amazonensis. Materials and Methods: The naphthotriazolyl-4-oxoquinoline derivatives were obtained in good to moderate yields via the [3+2] cycloaddition reaction between 1,4-naphtoquinone and azido-4- oxoquinoline derivatives. HMPA at 100°C was established as the best solvent and temperature condition for this reaction. The structures of the compounds were confirmed by spectral analyses (infrared spectroscopy, one- and two-dimensional ¹H and ¹³C NMR spectroscopy, and high-resolution mass spectrometry). The compounds exhibited promising activities with IC50 values ranging from 0.7 to 2.0 µM against intracellular amastigotes of Leishmania amazonensis. The most selective compound was the Npentyl- substituted derivative, which showed a Selectivity Index (SI) of 8.6, making it less toxic than pentamidine (SI 4.5). Results: Our results demonstrated that all compounds, except the N-propyl-substituted derivative, induce ROS production by parasites early in the culture. As a proof of concept, we demonstrated that the most selective compound was able to interfere with sterol biosynthesis in L. amazonensis. Conclusion: The naphthotriazolyl-4-oxoquinoline derivatives were obtained in good to moderate yields. These conjugates have potent in vitro antileishmanial activity involving at least two different mechanisms of action, making them promising lead compounds for the development of new therapeutic alternatives for leishmaniasis.

scholarly journals Activity of Cuban Propolis Extracts on Leishmania Amazonensis and Trichomonas vaginalis

2011 ◽  
Vol 6 (7) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Lianet Monzote Fidalgo ◽  
Idalia Sariego Ramos ◽  
Marley García Parra ◽  
Osmany Cuesta-Rubio ◽  
Ingrid Márquez Hernández ◽  
...  
Keyword(s):  
Trichomonas Vaginalis ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
Leishmania Amazonensis ◽  
Natural Source ◽  
Antiprotozoal Activity ◽  
Intracellular Amastigotes ◽  
Yellow Type

In this paper we analyzed the antiprotozoal effects of eighteen Cuban propolis extracts (brown, red and yellow type) collected in different geographic areas, using Leishmania amazonensis (as a model of intracellular protozoa) and Trichomonas vaginalis (as a model of extracellular protozoa). All evaluated propolis extracts caused inhibitory effect on intracellular amastigotes of L. amazonensis. However, cytotoxicity on peritoneal macrophages from BALB/c mice was observed. Only five samples decreased the viability of T. vaginalis trophozoites at concentrations lower than 10 μg/mL. No correlation between the type of propolis and antiprotozoal activity was found. Cuban propolis extracts demonstrated activity against both intracellular and extracellular protozoa model, as well as the potentialities of propolis as a natural source to obtain new antiprotozoal agents.

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