scholarly journals Synthesis, Cytotoxicity, and Antileishmanial Activity of N,N'-Disubstituted Ethylenediamine and Imidazolidine Derivatives

2010 ◽  
Vol 10 ◽  
pp. 1723-1730 ◽  
Author(s):  
Gustavo S. G. de Carvalho ◽  
Patrícia A. Machado ◽  
Daniela T. S. de Paula ◽  
Elaine S. Coimbra ◽  
Adilson D. da Silva
Keyword(s):  
Mammalian Cells ◽  
Biological Activities ◽  
Biological Membranes ◽  
Antileishmanial Activity ◽  
Good Activity ◽  
Polyamine Synthesis ◽  
Leishmanicidal Activity ◽  
Intracellular Amastigotes

This paper describes the preparation of N,N'-disubstituted ethylenediamine and imidazolidine derivatives and their in vitro biological activities againstLeishmaniaspecies. Of the nine synthesized compounds, five displayed a good activity in bothL. amazonensisandL. majorpromastigotes. The compounds 1,2-Bis(p-methoxybenzyl)ethylenediamine (4) and 1,3-Bis(p-methoxybenzyl)imidazolidines (5) showed the best activity on intracellular amastigotes, with IC50values of 2.0 and 9.4 μ/mL, respectively. In addition, none of compounds were cytotoxic against mammalian cells. The leishmanicidal activity can be related with inhibition of polyamine synthesis and cellular penetration within biological membranes.

scholarly journals Regulation of c-Fes Tyrosine Kinase and Biological Activities by N-Terminal Coiled-Coil Oligomerization Domains

1999 ◽  
Vol 19 (12) ◽  
pp. 8335-8343 ◽  
Author(s):  
Haiyun Cheng ◽  
Jim A. Rogers ◽  
Nancy A. Dunham ◽  
Thomas E. Smithgall
Keyword(s):  
Tyrosine Kinase ◽  
Mammalian Cells ◽  
Protein Tyrosine Kinase ◽  
Biological Activities ◽  
Coiled Coil ◽  
Protein Tyrosine ◽  
Coiled Coil Domain ◽  
Fibroblast Transformation

ABSTRACT The cytoplasmic protein-tyrosine kinase Fes has been implicated in cytokine signal transduction, hematopoiesis, and embryonic development. Previous work from our laboratory has shown that active Fes exists as a large oligomeric complex in vitro. However, when Fes is expressed in mammalian cells, its kinase activity is tightly repressed. The Fes unique N-terminal sequence has two regions with strong homology to coiled-coil-forming domains often found in oligomeric proteins. Here we show that disruption or deletion of the first coiled-coil domain upregulates Fes tyrosine kinase and transforming activities in Rat-2 fibroblasts and enhances Fes differentiation-inducing activity in myeloid leukemia cells. Conversely, expression of a Fes truncation mutant consisting only of the unique N-terminal domain interfered with Rat-2 fibroblast transformation by an activated Fes mutant, suggesting that oligomerization is essential for Fes activation in vivo. Coexpression with the Fes N-terminal region did not affect the transforming activity of v-Src in Rat-2 cells, arguing against a nonspecific suppressive effect. Taken together, these findings suggest a model in which Fes activation may involve coiled-coil-mediated interconversion of monomeric and oligomeric forms of the kinase. Mutation of the first coiled-coil domain may activate Fes by disturbing intramolecular coiled-coil interaction, allowing for oligomerization via the second coiled-coil domain. Deletion of the second coiled-coil domain blocks fibroblast transformation by an activated form of c-Fes, consistent with this model. These results provide the first evidence for regulation of a nonreceptor protein-tyrosine kinase by coiled-coil domains.

scholarly journals Synthesis and biological activities of some indoline derivatives

2009 ◽  
Vol 74 (12) ◽  
pp. 1377-1387 ◽  
Author(s):  
Milind Rode ◽  
Sahebrao Rindhe ◽  
Bhausaheb Karale
Keyword(s):  
Antioxidant Activity ◽  
Aromatic Amines ◽  
Benzoyl Chloride ◽  
Stannous Chloride ◽  
Biological Activities ◽  
Gram Negative Bacteria ◽  
Good Activity ◽  
Dpph Assay ◽  
Gram Negative

The reaction of indoline with a substituted benzoyl chloride in the presence of K2CO3 in THF gave compound 4. Compound 4 was subjected to chlorosulphonation to obtain compound 5. Condensation of aromatic amines with compound 5 led to the synthesis of indoline derivatives 6(a-f). Similarly, 5-nitroindoline was treated with a substituted benzoyl chloride to obtain the nitro compound 9, which was reduced using stannous chloride and reacted further with aromatic sulphonyl chloride to obtain the indoline derivatives 11(a-e). These compounds were tested for antibacterial, anti-tuberculosis and antifungal activity. Some of them showed very good activity against some gram-positive and gram negative bacteria, fungal strains and also Mycobacterium tuberculosis. All of the synthesized compounds were subjected to antioxidant activity testing using the in vitro DPPH assay and most of them showed very good activity.

scholarly journals Leishmanicidal Activity of Nine Novel Flavonoids fromDelphinium staphisagria

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Inmaculada Ramírez-Macías ◽  
Clotilde Marín ◽  
Jesús G. Díaz ◽  
María José Rosales ◽  
Ramón Gutiérrez-Sánchez ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Mammalian Cells ◽  
Mechanisms Of Action ◽  
Reference Drug ◽  
Ultrastructural Alteration ◽  
Leishmanicidal Activity ◽  
Design And Methods ◽  
Electronic Microscope ◽  
Intracellular Amastigote

Objectives. To evaluate thein vitroleishmanicidal activity of nine flavonoid derivatives fromDelphinium staphisagriaagainstL. infantumandL. braziliensis.Design and Methods. Thein vitroactivity of compounds1–9was assayed on extracellular promastigote and axenic amastigote forms and on intracellular amastigote forms of the parasites. Infectivity and cytotoxicity tests were carried on J774.2 macrophage cells using Glucantime as the reference drug. The mechanisms of action were analysed performing metabolite excretion and transmission electronic microscope ultrastructural alteration studies.Results. Nine flavonoids showed leishmanicidal activity against promastigote as well as amastigote forms ofLeishmania infantumandL. braziliensis. These compounds were nontoxic to mammalian cells and were effective at similar concentrations up to or lower than that of the reference drug (Glucantime). The results showed that2″-acetylpetiolaroside (compound8) was clearly the most active.Conclusion. This study has demonstrated that flavonoid derivatives are active againstL. infantumandL. braziliensis.

scholarly journals Double-blind, Randomized, Clinical Trial on the Antileishmanial Activity of a Morinda citrifolia (Noni) Stem Extract and its Major Constituents

2012 ◽  
Vol 7 (2) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Fouzia A. Sattar ◽  
Fayaz Ahmed ◽  
Nadeem Ahmed ◽  
Samina A. Sattar ◽  
Muhammad A. K Malghani ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Leishmania Major ◽  
Antileishmanial Activity ◽  
Morinda Citrifolia ◽  
Controlled Study ◽  
Good Activity ◽  
Double Blind ◽  
Stem Extract ◽  
Good Improvement

A controlled study was conducted to determine the efficiency of a topical ointment prepared from the stem extract of Morinda citrifolia against cutaneous leishmaniasis. Similarly, the in vitro antileishmanial activity of morindicone and morinthone isolated from the extract were investigated against Leishmania major. These compounds displayed good activity. Out of 40 patients, 50% showed an excellent response and 30% exhibited good improvement.

scholarly journals Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4960
Author(s):  
Olalla Barreiro-Costa ◽  
Gabriela Morales-Noboa ◽  
Patricio Rojas-Silva ◽  
Eliana Lara-Barba ◽  
Javier Santamaría-Aguirre ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
In Silico ◽  
Potential Application ◽  
Mammalian Cells ◽  
Biological Activities ◽  
Antioxidant Properties ◽  
Therapeutic Use ◽  
Derivatives Of

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

scholarly journals Synthesis and Antileishmanial Activity of Lipophilic Aromatic Aminoalcohols

2010 ◽  
Vol 10 ◽  
pp. 1067-1072 ◽  
Author(s):  
Roberta Novaes Reis Corrales ◽  
Liliane Sena Pinheiro ◽  
Elaine Soares Coimbra ◽  
Adilson David Da Silva ◽  
Mireille Le Hyaric
Keyword(s):  
Antiproliferative Activity ◽  
Leishmania Species ◽  
Antileishmanial Activity ◽  
Good Activity ◽  
Preparation And Evaluation

In this work, we report on the preparation and evaluation of thein vitroantileishmanial activity of a series of lipophilic aromatic aminoalcohols. All compounds were assessed for theirin vitroactivity against promastigotes of threeLeishmania speciesThe most lipophilic aminoalcohols bearing an aliphatic moiety with eight to 12 carbon atoms displayed a good activity againstL. amazonensisandL. major, and two of them also showed antiproliferative activity againstL. chagasi. The best results were obtained for the N-dodecanoyl ethylenediamine derivative and for N-decyl aminoalcohol (IC50= 5.2 and 0.7μM, respectively).

scholarly journals The Antiaging Effect of Active Fractions and Ent-11α-Hydroxy-15-Oxo-Kaur-16-En-19-Oic Acid Isolated from Adenostemma lavenia (L.) O. Kuntze at the Cellular Level

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 719
Author(s):  
Irmanida Batubara ◽  
Rika Indri Astuti ◽  
Muhammad Eka Prastya ◽  
Auliya Ilmiawati ◽  
Miwa Maeda ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Biological Activities ◽  
Antioxidant Properties ◽  
In Vitro Assays ◽  
Mitochondrial Activity ◽  
Related Factor ◽  
Dependent Manner ◽  
B16f10 Cells ◽  
Anti Inflammatory

Background: The extract of Adenostemma lavenia (L.) O. Kuntze leaves has anti-inflammatory activities and is used as a folk medicine to treat patients with hepatitis and pneumonia in China and Taiwan. The diterpenoid ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (11αOH-KA) is the major ingredient in the extract and has wide-spectrum biological activities, such as antitumor and antimelanogenic activities, as well as anti-inflammatory activity. However, the physical and biological properties of this compound as an antioxidant or antiaging agent have not been reported yet. Methods: In addition to in vitro assays, we monitored antioxidative and antiaging signals in Schizosaccharomyces pombe (yeast) and mouse melanoma B16F10 cells. Results: A. lavenia water and chloroform fractions showed antioxidant properties in vitro. The A. lavenia extracts and 11αOH-KA conferred resistance to H2O2 to S. pombe and B16F10 cells and extended the yeast lifespan in a concentration-dependent manner. These materials maintained the yeast mitochondrial activity, even in a high-glucose medium, and induced an antioxidant gene program, the transcriptional factor pap1+ and its downstream ctt1+. Accordingly, 11αOH-KA activated the antioxidative transcription factor NF-E2-related factor 2, NRF2, the mammalian ortholog of pap1+, in B16F10 cells, which was accompanied by enhanced hemeoxygenase expression levels. These results suggest that 11αOH-KA and A. lavenia extracts may protect yeast and mammalian cells from oxidative stress and aging. Finally, we hope that these materials could be helpful in treating COVID-19 patients, because A. lavenia extracts and NRF2 activators have been reported to alleviate the symptoms of pneumonia in model animals.

scholarly journals Evaluation of theIn VitroAntiplasmodial, Antileishmanial, and Antitrypanosomal Activity of Medicinal Plants Used in Saudi and Yemeni Traditional Medicine

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ramzi A. Mothana ◽  
Nawal M. Al-Musayeib ◽  
Mohamed F. Al-Ajmi ◽  
Paul Cos ◽  
Louis Maes
Keyword(s):  
Medicinal Plants ◽  
High Selectivity ◽  
Moderate Activity ◽  
Good Activity ◽  
Antiprotozoal Activity ◽  
Traditional Use ◽  
Active Constituents ◽  
Intracellular Amastigotes ◽  
Antitrypanosomal Activity

The antiplasmodial, antileishmanial, and antitrypanosomal activity of twenty-five medicinal plants distributed in Saudi Arabia and Yemen was evaluated. The plants were extracted with methanol and screenedin vitroagainst erythrocytic schizonts ofPlasmodium falciparum, intracellular amastigotes ofLeishmania infantumandTrypanosoma cruzi, and free trypomastigotes ofT. brucei. To assess selectivity, cytotoxicity was determined on MRC-5 cells. Criteria for activity were anIC50<10 μg/mL and high selectivity (SI). Seven plants showed interesting antiprotozoal activity in one or more models. Extracts ofCaralluma penicillataandAcalypha ciliatashowed fairly good activity againstP. falciparumwith IC50of 6.7 and 10.8 μg/mL and adequate selectivity (SI>9.6and>5.9). Interesting activity againstL. infantumwas obtained withVerbascum bottae(IC50of 3.2 μg/mL, SI 10.2) andSolanum glabratum(IC508.1 μg/mL, SI 3.4). The extracts ofC. penicillata, Leucas virgata, Loranthus regularis, andV. bottaeexhibited moderate activity againstT. brucei(IC508.5, 8.1, 8.3, and 2.3 μg/mL;SI>7.6, 7.7, 4.3, and>14.1). These results partly support the traditional use of some of the selected medicinal plants and warrant further investigations into the putative active constituents.

scholarly journals Novel Dual Acting Antimalarial Antileishmanial Agents Derived from Pyrazole Moiety

2021 ◽  
Vol 12 (5) ◽  
pp. 6225-6233
Keyword(s):  
Molecular Docking ◽  
Survival Time ◽  
Antimalarial Activity ◽  
Biological Activities ◽  
Pyrazole Ring ◽  
Antileishmanial Activity ◽  
Pyrazole Derivatives ◽  
Mean Survival Time

Malaria and leishmaniasis are two highly detrimental parasitic diseases with a global impact. Attempts to eradicate malaria and control leishmaniasis are generally unsuccessful due to the rapidly developing resistance to currently used drug therapy. The pyrazole ring is a key moiety reported to have a variety of biological activities. The current study aimed to design, synthesize and evaluate an array of pyrazole derivatives for potential antimalarial antileishmanial activity. The scheme for the synthesis of the pyrazole derivatives is presented. The antimalarial activity was assessed in-vivo on P. berghei ANKA infected mice to determine % parasitemia and mean survival time. The antileishmanial activity was assessed in-vitro, and IC50 for each compound was calculated. In-vivo acute toxicity and molecular docking on putative antimalarial and antileishmanial drug targets were performed using the most active compounds. All the derivatives exhibited significant antimalarial activity, the highest being 95% suppression of parasitemia with compounds 9a and 9b. The mean survival time of mice treated with these two compounds was also the highest (16-17 days) but was lower than chloroquine, the standard agent. Compounds 9a and 9b exhibited superior antileishmanial activity as compared to miltefosine. However, they were less potent than amphotericin. The compounds were safe and well-tolerated at toxic, oral and intraperitoneal, doses of 150mg/kg and 75mg/kg, respectively. Molecular docking of compound 9a revealed a good fitting pose with plasmodial Pf-DHFR enzyme and Lm-PTR1 enzyme, which explains the biological activity noted with this compound. Pyrazole derivatives 9a and 9b exhibited substantial dual antimalarial antileishmanial activity and may be a valuable scaffold for the design of further derivatives with antiprotozoal potential.

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