scholarly journals In Vitro Activities of 7-Substituted 9-Chloro and 9-Amino-2-Methoxyacridines and Their Bis- and Tetra-Acridine Complexes against Leishmania infantum

2003 ◽  
Vol 47 (1) ◽  
pp. 174-180 ◽  
Author(s):  
Carole Di Giorgio ◽  
Florence Delmas ◽  
Nathalie Filloux ◽  
Maxime Robin ◽  
Laetitia Seferian ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Dna Synthesis ◽  
Leishmania Infantum ◽  
Antileishmanial Activity ◽  
Human Monocytes ◽  
Secondary Effects ◽  
Dna Metabolism ◽  
Biochemical Pathways ◽  
Main Target

ABSTRACT 9-Chloro and 9-amino-2-methoxyacridines bearing different substituents in position 7, as well as their corresponding unsubstituted dimeric and tetrameric complexes, were investigated for in vitro antiproliferative properties against Leishmania infantum compared to toxicity towards human monocytes. The results clearly confirmed that several compounds of the 2-methoxyacridine series, together with their corresponding dimeric and tetrameric derivatives, had strong in vitro antiparasitic properties. Antileishmanial activity was shown to depend on the nature of both 7- and 9-substituted groups in monoacridines, while it varied according to the nature of the 9-substituted group and the length of the linker among bis- and tetra-acridines. The effects of acridine derivatives on DNA synthesis raised the hypothesis that DNA metabolism constituted their main target in Leishmania promastigotes; however, secondary effects on other biochemical pathways, including protein and lipid metabolism, were observed, suggesting that acridine compounds could be considered multitarget drugs.

scholarly journals The effect of sinefungin on the macromolecular biosynthesis of Leishmania species

2018 ◽  
Vol 49 (2) ◽  
pp. 137
Author(s):  
A. TZORA (Α. ΤΖΩΡΑ) ◽  
F. LAWRENCE ◽  
M. ROBERT-GERO
Keyword(s):  
Dna Synthesis ◽  
Mode Of Action ◽  
Rna Synthesis ◽  
In Vitro Study ◽  
Leishmania Species ◽  
Sensitive Strain ◽  
Vitro Study ◽  
No Inhibition ◽  
Main Target

The aim of the work presented here was the in vitro study of the action of the antibiotic sinefungin on the macromolecules DNA, RNA and the proteins of different isolates of Leismannia spp. in relation to the resistance or to the sensitivity of the strains examined. The mode of action of sinefungin of the Leishmania strains was detected by incorporating radiolabeled thymidine, uridine and leucine into promastigote forms, to study the synthesis of DNA, RNA and proteins respectively. In the sensitive strain L. tropica a statistically significant reduction of the rate of incorporation of thymidine to the DNA of the parasite, resulted to a 64% inhibition of leishmanial DNA synthesis by sinefungin at a concentration of 2.6 mM, when the time of action of the drug was 24 hours. In the sensitive strain L. tropica the reduction of the rate of incorporation of thymidine was depended on the concentration and the time of action of the drug. No inhibition of leishmanial RNA synthesis was observed. Our research showed that the action of the antibiotic sinefungin to the macromolecular biosynthesis of the protozoan Leishmania is independent of the strain and is strongly related with the expression of the sensitivity and the resistance of the strain. The main target of the antibiotic examined was the DNA of the Leishmania strains sensitive to the drug.

scholarly journals Ultrastructural Analysis ofLeishmania infantum chagasiPromastigotes Forms TreatedIn Vitrowith Usnic Acid

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
João S. B. da Luz ◽  
Erwelly B. de Oliveira ◽  
Monica C. B. Martins ◽  
Nicácio H. da Silva ◽  
Luiz C. Alves ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Usnic Acid ◽  
Public Health Problem ◽  
Ultrastructural Analysis ◽  
Antileishmanial Activity ◽  
World Health ◽  
Global Public Health ◽  
Drug Induced ◽  
Leishmania Infantum Chagasi

Leishmaniasis is considered by the World Health Organization as one of the infectious parasitic diseases endemic of great relevance and a global public health problem. Pentavalent antimonials used for treatment of this disease are limited and new phytochemicals emerge as an alternative to existing treatments, due to the low toxicity and cost reduction. Usnic acid is uniquely found in lichens and is especially abundant in genera such asAlectoria,Cladonia,Evernia,Lecanora,Ramalina,andUsnea. Usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti-inflammatory, and analgesic activity. The aim of this study was to evaluate the antileishmanial activity of usnic acid onLeishmania infantum chagasipromastigotes and the occurrence of drug-induced ultrastructural damage in the parasite. Usnic acid was effective against the promastigote forms (IC50= 18.30 ± 2.00 µg/mL). Structural and ultrastructural aspects of parasite were analyzed. Morphological alterations were observed as blebs in cell membrane and shapes given off, increasing the number of cytoplasmic vacuoles, and cellular and mitochondrial swelling, with loss of cell polarity. We concluded that the usnic acid presented antileishmanial activity against promastigote forms ofLeishmania infantum chagasiand structural and ultrastructural analysis reinforces its cytotoxicity. Further,in vitrostudies are warranted to further evaluate this potential.

scholarly journals First example of peptides targeting the dimer interface of Leishmania infantum trypanothione reductase with potent in vitro antileishmanial activity #

2017 ◽  
Vol 135 ◽  
pp. 49-59 ◽  
Author(s):  
Marta Ruiz-Santaquiteria ◽  
Pedro A. Sánchez-Murcia ◽  
Miguel A. Toro ◽  
Héctor de Lucio ◽  
Kilian Jesús Gutiérrez ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Antileishmanial Activity ◽  
Trypanothione Reductase ◽  
Dimer Interface

scholarly journals Ivermectin presents effective and selective antileishmanial activity in vitro and in vivo against Leishmania infantum and is therapeutic against visceral leishmaniasis

2021 ◽  
Vol 221 ◽  
pp. 108059
Author(s):  
Thiago A.R. Reis ◽  
João A. Oliveira-da-Silva ◽  
Grasiele S.V. Tavares ◽  
Débora V.C. Mendonça ◽  
Camila S. Freitas ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Antileishmanial Activity

scholarly journals Development of Nanoemulsions to Enhance the Antileishmanial Activity ofCopaifera pauperaOleoresins

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Igor A. Rodrigues ◽  
Aline de S. Ramos ◽  
Deborah Q. Falcão ◽  
José Luiz P. Ferreira ◽  
Silvia L. Basso ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Leishmania Amazonensis ◽  
Antileishmanial Activity ◽  
First Report ◽  
Crude Extracts

Based on the ethnopharmacological evidences about the antileishmanial activity ofCopaiferaspp. oleoresins, the effects of crude extracts and fractions of oleoresin of two specimens fromCopaifera pauperawere evaluated onLeishmania amazonensisandLeishmania infantumstrains. The oleoresin rich inα-copaene (38.8%) exhibited the best activity againstL. amazonensis(IC50= 62.5 μg/mL) and againstL. infantum(IC50= 65.9 μg/mL). The sesquiterpeneα-copaene isolated was tested alone and exhibited high antileishmanial activityin vitrowith IC50values forL. amazonensisandL. infantumof 17.2 and 11.4 μg/mL, respectively. In order to increase antileishmanial activity, nanoemulsions containing copaiba oleoresin andα-copaene were developed and assayed againstL. amazonensisandL. infantumpromastigotes. The nanoemulsion containingα-copaene (NANOCOPAEN) showed the best activity against both species, with IC50of 2.5 and 2.2 μg/mL, respectively. This is the first report about the antileishmanial activity ofα-copaene.

In vitro and in vivo antileishmanial activity of a fluoroquinoline derivate against Leishmania infantum and Leishmania amazonensis species

Acta Tropica ◽  
2019 ◽  
Vol 191 ◽  
pp. 29-37 ◽  
Author(s):  
Grasiele S.V. Tavares ◽  
Débora V.C. Mendonça ◽  
Daniela P. Lage ◽  
Luciana M.R. Antinarelli ◽  
Tauane G. Soyer ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Leishmania Amazonensis ◽  
Antileishmanial Activity

scholarly journals Acarbose presents in vitro and in vivo antileishmanial activity against Leishmania infantum and is a promising therapeutic candidate against visceral leishmaniasis

2021 ◽  
Author(s):  
Rafaella R. Costa ◽  
João A. Oliveira-da-Silva ◽  
Thiago A. R. Reis ◽  
Grasiele S. V. Tavares ◽  
Débora V. C. Mendonça ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Antileishmanial Activity

Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

1983 ◽  
Vol 50 (04) ◽  
pp. 804-809 ◽  
Author(s):  
Torstein Lyberg
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Immune Complexes ◽  
Phosphodiesterase Inhibitors ◽  
Inhibitory Effect ◽  
Intracellular Camp ◽  
Human Monocytes ◽  
Purified Protein Derivative ◽  
A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

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