Leishmanicidal Activity of Artemisinin, Deoxoartemisinin, Artemether and Arteether

In this work we studied the in vitro toxicity of artemisinin and its chemical derivatives deoxoartemisinin, artemether and arteether against stationary phase promastigotes of Leishmania (L) mexicana. Results presented in this work include dramatic changes in parasite morphology when they were cultured in the presence of these chemicals. These changes were accompanied by the parasite's lost of mobility and eventual death after four days of culturing. We also observed that parasite growth was much more effectively reduced in cultures carried out in the presence of either artemisinin or its semi-synthetic derivatives than the reference drug N-methyl meglumine (Glucantime™, Rhone Poulenc, France). The compounds tested in this work were not toxic to Hela cells cultured in vitro. This is the first report describing the promising potential use of Qinghaosu (artemisinin) and related chemical analogues to treat L (L) mexicana infections.

Download Full-text

Leishmanicidal activity of racemic ± 8-[(4-Amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline

Natural Product Communications ◽

10.1177/1934578x1000500309 ◽

2010 ◽

Vol 5 (3) ◽

pp. 1934578X1000500 ◽

Cited By ~ 2

Author(s):

Angélica P. Isaac-Márquez ◽

James D. McChesney ◽

N.P. Dammika Nanayakara ◽

Abhay R. Satoskar ◽

Claudio M. Lezama-Dávila

Keyword(s):

Stationary Phase ◽

Hela Cells ◽

Parasite Growth ◽

In Vitro Toxicity ◽

Reference Drug ◽

Leishmanicidal Activity ◽

First Report ◽

Cells Cultured

In this work we studied the in vitro toxicity of ± 8-[(4-Amino-1-Methylbutyl)Amino]-6-Methoxy-4-Methyl-5-[3,4-dichlorophenoxy]quinoline (DN3-27-1) against stationary phase promastigotes Leishmania (L.) mexicana. Our results indicate that this drug induces an important reduction in parasite growth and killing compared to the reference drug N-methyl meglumine (Glucantime™). DN3-27-1 was not toxic to Hela cells cultured in vitro. This is the first report describing the promising potential of DN3-27-1 in treatment of L. ( L.) m exicana infections.

Download Full-text

Manipulation of the phenotype of immortalised rat hepatocytes by different culture configurations and by dimethyl sulphoxide

Human & Experimental Toxicology ◽

10.1191/096032700678815936 ◽

2000 ◽

Vol 19 (5) ◽

pp. 309-317 ◽

Cited By ~ 11

Author(s):

M I Grant ◽

K Anderson ◽

G McKay ◽

M Wills ◽

C Henderson ◽

...

Keyword(s):

Primary Cultures ◽

Toxicity Testing ◽

Normal Liver ◽

Rat Hepatocytes ◽

In Vitro Toxicity ◽

Collagen Gels ◽

Testosterone Metabolism ◽

Glutathione S Transferases ◽

Cells Cultured

The liver-specific phenotype of immortalised rat hepato-cytes is not irretrievably lost as they age in culture but can be manipulated by modifying the culture environment. Testosterone metabolism was used to investigate the profile of cytochrome P450 isoenzymes present in two immortalised cell lines, P9 and LQC, and in primary cultures of rat hepatocytes, cultured on collagen films, gels and double gel cultures (sandwich configuration). The extent of testosterone metabolism, and the range of metabolites produced, was increased in immortalised cells by the presence of collagen as a substratum film or gel but survival was poorer and the range of metabolites was reduced in sandwich culture. In contrast, testosterone metabolism was retained in primary hepatocytes in sandwich cultures at a higher level than in collagen film or gel cultures. Expression of alpha class glutathione-S-transferases (GSTs) increased and that of GSTP1 decreased (changes which indicate a recovery of normal liver GST phenotype) when the medium of immortalised cell cultures was supplemented with dimethyl sulph-oxide (DMSO). DMSO also improved ethoxyresorufin 0-deethylation (EROD) and testosterone metabolism in immortalised cells. It also markedly inhibited prolifera-tion, DNA, RNA and protein synthesis. Maximal testosterone metabolism was observed in immortalised cells cultured on collagen gels in the presence of l1o (v/v) DMSO. Development of a protocol for treating immortalised liver cells cultured on collagen gels with DMSO to switch between proliferation and differentiation may provide a convenient system expres-sing the xenobiotic metabolising enzymes required for in vitro toxicity testing.

Download Full-text

In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652011000300003 ◽

2011 ◽

Vol 53 (3) ◽

pp. 129-132 ◽

Cited By ~ 12

Author(s):

Joshua Muli Mutiso ◽

John Chege Macharia ◽

Mustafa Barasa ◽

Evans Taracha ◽

Alain J. Bourdichon ◽

...

Keyword(s):

Leishmania Donovani ◽

Combined Therapy ◽

Parasite Burden ◽

Mice Model ◽

In Vivo Evaluation ◽

Reference Drug ◽

Drug Treatments ◽

Potential Use

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

Download Full-text

On the Shape of the Dose-response Curve for HeLa Cells cultured in vitro and exposed to Gamma-radiation

Nature ◽

10.1038/2091363a0 ◽

1966 ◽

Vol 209 (5030) ◽

pp. 1363-1364 ◽

Cited By ~ 8

Author(s):

JOEL S. BEDFORD ◽

ERIC J. HALL

Keyword(s):

Gamma Radiation ◽

Dose Response ◽

Hela Cells ◽

Response Curve ◽

Dose Response Curve ◽

Cells Cultured

Download Full-text

Beyond platinum: synthesis, characterization, and in vitro toxicity of Cu(II)-releasing polymer nanoparticles for potential use as a drug delivery vector

Nanoscale Research Letters ◽

10.1186/1556-276x-6-445 ◽

2011 ◽

Vol 6 (1) ◽

pp. 445 ◽

Cited By ~ 4

Author(s):

Alesha N Harris ◽

Barbara R Hinojosa ◽

Montaleé D Chavious ◽

Robby A Petros

Keyword(s):

Drug Delivery ◽

Polymer Nanoparticles ◽

In Vitro Toxicity ◽

Delivery Vector ◽

Potential Use

Download Full-text

In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry

Antioxidants ◽

10.3390/antiox8100467 ◽

2019 ◽

Vol 8 (10) ◽

pp. 467 ◽

Cited By ~ 6

Author(s):

Concepción Medrano-Padial ◽

María Puerto ◽

F. Javier Moreno ◽

Tristan Richard ◽

Emma Cantos-Villar ◽

...

Keyword(s):

Antimicrobial Activities ◽

Toxicity Assessment ◽

Wine Industry ◽

In Vitro Toxicity ◽

Toxicological Assessment ◽

Significant Damage ◽

Significant Impairment ◽

In Vitro Toxicity Assessment ◽

Potential Use

The reduction of sulfur dioxide in wine is a consumer’s demand, considering the allergic effects that may occur in people who are sensitive to it. Stilbenes are candidates of great interest for this purpose because of their antioxidant/antimicrobial activities and health properties, and also because they are naturally found in the grapevine. In the present study, the in vitro toxicity of an extract from grapevine shoots (with a stilbene richness of 45.4%) was assessed in two human cell lines. Significant damage was observed from 30 μg/mL after 24 h, and 40 µg/mL after 48 h of exposure. Similarly, the ultrastructural study revealed a significant impairment of cell growing. The extract was able to protect cells against an induced oxidative stress at all concentrations studied. In view of the promising results, a more exhaustive toxicological assessment of the extract is needed to confirm the safety of its further use as additive in wine.

Download Full-text

Antiglycoxidative Properties of Extracts and Fractions from Reynoutria Rhizomes

Nutrients ◽

10.3390/nu13114066 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4066

Author(s):

Arleta Dołowacka-Jóźwiak ◽

Adam Matkowski ◽

Izabela Nawrot-Hadzik

Keyword(s):

Amyloid Β ◽

Herbal Products ◽

Reference Drug ◽

Reynoutria Japonica ◽

Glycation End Products ◽

Long Time ◽

Treatment Of Diabetes ◽

Cellular Abnormalities ◽

Potential Use

Hyperglycemia, when sustained over a long time in diabetes mellitus (DM), leads to biochemical and cellular abnormalities, primarily through the formation of advanced glycation end-products (AGEs). In the treatment of diabetes, beside blood-sugar-lowering medications, a consumption of herbal products that can inhibit the AGEs’ formation is recommended. This study investigated the in vitro antiglycoxidative potential of extracts and fractions from the rhizomes of Japanese, Giant, and Bohemian knotweeds (Reynoutria japonica (Houtt.), R. sachalinensis (F. Schmidt) Nakai, and R.× bohemica Chrtek et Chrtkova). Their effects on glycooxidation of bovine and human serum albumin were evaluated by incubation of the proteins with a mixture of glucose and fructose (0.5 M) and 150 µg/mL of extract for 28 days at 37 °C, followed by measuring early and late glycation products, albumin oxidation (carbonyl and free thiol groups), and amyloid-β aggregation (thioflavin T and Congo red assays). The highest antiglycoxidative activity, comparable or stronger than the reference drug (aminoguanidine), was observed for ethyl acetate and diethyl ether fractions, enriched in polyphenols (stilbenes, phenylpropanoid disaccharide esters, and free and oligomeric flavan-3-ols). In conclusion, the antiglycoxidative compounds from these three species should be further studied for potential use in the prevention and complementary treatment of DM.

Download Full-text

The Use of Human Lymphocytes for the In Vitro Estimation of Acute Toxicity of Ten Chemicals from the MEIC List

Alternatives to Laboratory Animals ◽

10.1177/026119299101900206 ◽

1991 ◽

Vol 19 (2) ◽

pp. 187-190

Author(s):

Mette Tingleff Skaanild ◽

Jørgen Clausen

Keyword(s):

Hela Cells ◽

Cultured Cells ◽

Human Lymphocytes ◽

Primary Cultures ◽

Biological Significance ◽

In Vitro Cytotoxicity ◽

In Vitro Toxicity ◽

Human Hepatoma Cells ◽

Response Curves

The acute cytotoxicity of ten chemicals included in the MEIC (multicentre evaluation of in vitro cytotoxicity) list has already been estimated in various cell lines, e.g. primary rat hepatocytes, HeLa cells, human hepatoma cells, and 3T3 and mouse fibroma cells. In the present study, primary cultures of human lymphocytes, with or without an S9-mix (microsomes), were used to assay for in vitro toxicity. The cultured cells were initially treated with different concentrations of the respective drugs for 24 hours. Then cellular enzymatic activity was estimated using two assay systems, namely, measurement of cytosolic LDH activity and the mitochondrial (diaphorase) MTT test. Since the biological significance of the assay of LC50 values is dependent upon the slope of the dose-response curves, the results are expressed as LC20, LC50 and LC80 values in μM for the ten drugs. A Spearman rank correlation analysis revealed a significant correlation between the results from the two assays in both cell culture systems (r=1.00 and r=0.99). The LC50 values found in the lymphocyte cultures, both with and without an S9-mix, correlated well with the results previously found using primary cultures of hepatocytes and HeLa cells.

Download Full-text

Synthesis and Biological Profiles of Some Benzimidazolyl-chalcones as Anti-leishmanial and Trypanocidal Agents

Chemical Science International Journal ◽

10.9734/csji/2021/v30i830249 ◽

2021 ◽

pp. 47-56

Author(s):

D. U. J-P. N'Guessan ◽

L. A. C. Kablan ◽

A. Kacou ◽

C. Bories ◽

S. Coulibaly ◽

...

Keyword(s):

Trypanosoma Brucei ◽

Leishmania Donovani ◽

Parasite Growth ◽

Drug Candidate ◽

Trypanosoma Brucei Brucei ◽

Reference Drug ◽

Starting Point ◽

Ic50 Values ◽

Chlorine Derivative

Background: Benzimidazole constitutes a starting point for the development of new antiprotozoal agents since this nucleus exists in several pharmacologically significant molecules, in particular possessing antifungal, antiviral, antibacterial, and antiparasitic properties. Objective: The present study aimed to identify a molecular hit likely to be developed as an anti-leishmanial and antitrypanosomal drug candidate. Methods: Thus, 12 hybrids of chalcone or benzimidazolyl-arylpropenones were synthesized and screened in vitro for anti-leishmanial activity against promastigotes of Leishmania donovani. The microculture tetrazolium assay was used to determine their potential to inhibit 50% of a parasite growth (IC50). Results: Two compounds among 5-chlorobenzimidazole-chalcones (4a and 4c), which exhibited potent activity (IC50<1 μM) against L. donovani and one derivative (4d) poorly effective against L. donovani (IC50>50 μM) were selected to check their trypanocidal activity. Lethal concentration (LC100) values of these compounds were estimated by using observations on the viability of trypomastigotes of Trypanosoma brucei brucei in MEM medium with Earle’s salts and L-glutamine. Seven of the tested compounds (4a, 4b, 4c, 4e, 4g, 4h, and 4j) showed particularly higher inhibitory activity than pentamidine (IC50= 7.6 μM) against L. donovani promastigotes with IC50 values in a range from 0.5 to 1.8 μM. In addition, the 2’-chlorine derivative (4c), displayed potent anti-trypanosomal activity comparable to those of melarsoprol, used as reference drug. Conclusion: These results support this series of benzimidazole holding arylpropenone group in position 2 as a starting point for future optimization to get novel agents active against leishmaniasis and trypanosomiasis.

Download Full-text