scholarly journals Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Mauricio Peixoto Cupello ◽  
Francis Monique Saraiva ◽  
Pedro Ippolito ◽  
Andréia da Silva Fernandes ◽  
Rubem Figueiredo Sadoko Menna-Barreto ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
High Selectivity ◽  
Peritoneal Macrophages ◽  
Parasite Growth ◽  
Selectivity Index ◽  
Mutagenic Potential ◽  
Intracellular Amastigotes ◽  
In Vivo Tests ◽  
Harmful Effects

The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, againstTrypanosoma cruziforms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50=259.4±6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50=188.2±47.5 μM), with no harmful effects upon the mammalian cells (CC50values greater than 4 mM), resulting in a high selectivity index (CC50/IC50> 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50of about191.8±10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50of255.1±3.6 μM. Finally, we investigated the mutagenic potential of the nitrone by theSalmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 μM. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms ofT. cruzi, offering new insights into CD treatment suggesting additional in vivo tests.

Synthesis and characterization of novel dimerics-triazine derivatives as potential anti-bacterial agents against MDR clinical isolates

2018 ◽  
Vol 42 (13) ◽  
pp. 10676-10688 ◽  
Author(s):  
Doaa R. Ramadan ◽  
Aly A. Elbardan ◽  
Adnan A. Bekhit ◽  
Ayman El-Faham ◽  
Sherine N. Khattab
Keyword(s):  
Antimicrobial Activity ◽  
Schiff Bases ◽  
Mammalian Cells ◽  
High Selectivity ◽  
Bacterial Activity ◽  
Selectivity Index ◽  
Synthesis And Characterization ◽  
Triazine Derivatives ◽  
Ampicillin Trihydrate

Several dimerics-triazine Schiff bases displayed more potent anti-bacterial activity compared with ampicillin trihydrate. They revealed significantly low MIC values towards the tested MDR strains and showed a high selectivity index towards antimicrobial activity againstK. pneumoniaeandMRSA1compared to mammalian cells.

scholarly journals Synthesis and Antimalarial Activities of Cyclen 4-Aminoquinoline Analogs

2009 ◽  
Vol 53 (4) ◽  
pp. 1320-1324 ◽  
Author(s):  
M. O. Faruk Khan ◽  
Mark S. Levi ◽  
Babu L. Tekwani ◽  
Shabana I. Khan ◽  
Eiichi Kimura ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
High Selectivity ◽  
Antimalarial Activity ◽  
New Class ◽  
Antimalarial Agents ◽  
Sensitive Clone ◽  
Resistant Strains ◽  
Incorporation Assay

ABSTRACT In an attempt to augment the efficacy of 7-chloro 4-aminoquinoline analogs and also to overcome resistance to antimalarial agents, we synthesized three cyclen (1,4,7,10-tetraazacyclododecane) analogs of chloroquine [a bisquinoline derivative, 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline HBr, and a 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline-Zn2+ complex]. The bisquinoline displays the most potent in vitro and in vivo antimalarial activities. It displays 50% inhibitory concentrations (IC50s) of 7.5 nM against the D6 (chloroquine-sensitive) clone of Plasmodium falciparum and 19.2 nM against the W2 (chloroquine-resistant) clone, which are comparable to those of artemisinin (10.6 and 5.0 nM, respectively) and lower than those of chloroquine (10.7 and 87.2 nM, respectively), without any evidence of cytotoxicity to mammalian cells, indicating a high selectivity index (>1,333 against D6 clone and >521 against W2 clone). Potent antimalarial activities of the bisquinoline against chloroquine- and mefloquine-resistant strains of P. falciparum were also confirmed by in vitro [3H]hypoxanthine incorporation assay. The in vivo antimalarial activity of the bisquinoline, as determined in P. berghei-infected mice, is comparable to that of chloroquine (50% effective dose, ≤1.1 mg/kg when given orally); no apparent toxicity has been observed up to the highest dose tested (3 × 30 mg/kg). The bisquinoline inhibits in vitro hemozoin (β-hematin) formation with an IC50 of 1.1 μM, which is about 10-fold more potent than chloroquine (IC50 9.5 μM). Overall, this article describes the discovery of a new class of cyclen 4-aminoquinoline analogs as potent antimalarial 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.)

scholarly journals Antimalarial Activity of Simalikalactone E, a New Quassinoid from Quassia amara L. (Simaroubaceae)

2009 ◽  
Vol 53 (10) ◽  
pp. 4393-4398 ◽  
Author(s):  
N. Cachet ◽  
F. Hoakwie ◽  
S. Bertani ◽  
G. Bourdy ◽  
E. Deharo ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Inhibitory Concentration ◽  
Antimalarial Activity ◽  
Selectivity Index ◽  
Strain Sensitivity ◽  
Isolation And Identification ◽  
Quassia Amara ◽  
Plasmodium Vinckei

ABSTRACT We report the isolation and identification of a new quassinoid named simalikalactone E (SkE), extracted from a widely used Amazonian antimalarial remedy made out of Quassia amara L. (Simaroubaceae) leaves. This new molecule inhibited the growth of Plasmodium falciparum cultured in vitro by 50%, in the concentration range from 24 to 68 nM, independently of the strain sensitivity to chloroquine. We also showed that this compound was able to decrease gametocytemia with a 50% inhibitory concentration sevenfold lower than that of primaquine. SkE was found to be less toxic than simalikalactone D (SkD), another antimalarial quassinoid from Q. amara, and its cytotoxicity on mammalian cells was dependent on the cell line, displaying a good selectivity index when tested on nontumorogenic cells. In vivo, SkE inhibited murine malaria growth of Plasmodium vinckei petteri by 50% at 1 and 0.5 mg/kg of body weight/day, by the oral or intraperitoneal routes, respectively. The contribution of quassinoids as a source of antimalarial molecules needs therefore to be reconsidered.

Identification of toxic mineral dusts using mammalian cells

1980 ◽  
Vol 71 (3) ◽  
pp. 181-184 ◽  
Author(s):  
R. Davies ◽  
M. Chamberlain ◽  
R. C. Brown ◽  
D. M. Griffiths
Keyword(s):  
Cell Line ◽  
Mammalian Cells ◽  
Chinese Hamster ◽  
Cell Types ◽  
Peritoneal Macrophages ◽  
Alveolar Type ◽  
Mineral Dusts ◽  
Potential Pathogenicity

ABSTRACTCell culture systems have been developed to assess the potential pathogenicity of mineral dusts. The in vitro cytotoxicities of a variety of dusts towards mouse peritoneal macrophages, Chinese hamster lung cells (V79 cell line) and human alveolar type II cells (A549 cell line) were investigated.Non-pathogenic dusts were found to be inert in vitro. Fibrogenic non-fibrous dusts such as silica were only cytotoxic towards macrophages. Fibrous dusts which are both fibrogenic and carcinogenic in vivo are cytotoxic towards all three cell types, their cytotoxicity being dependent on fibre size. The size range important for the observed biological effect is longer than about 8 μm and thinner than about 1·5 μm.

scholarly journals Composition of nanoclay supported silver nanoparticles in furtherance of mitigating cytotoxicity and genotoxicity

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247531
Author(s):  
Chih-Hao Chang ◽  
Yu-Hsuan Lee ◽  
Zhen-Hao Liao ◽  
Mark Hung-Chih Chen ◽  
Fu-Chuo Peng ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Mammalian Cells ◽  
High Surface ◽  
High Surface Area ◽  
Weight Ratio ◽  
Geometric Dimension ◽  
Micronucleus Assay ◽  
Mutagenic Potential ◽  
Mtt Tests

Silver nanoparticle (Ag-NP) is well known for its high antibacterial efficacy. However, its toxicity toward mammalian cells is still a concern in clinical applications. The aim of our study was to evaluate the composition effects of Ag-NP supported by silicate nanoplatelet (NSP) with respect to the cytotoxicity and genotoxicity, and was in reference to the poly (styrene-co-maleic anhydride)-supported Ag-NP (Ag-NP/SMA). The NSP at the geometric dimension of averaged 80 x 80 x 1 nm3 was prepared from the exfoliation of natural clays and used to support different weight ratio of Ag-NP. The supporting limitation of NSP on Ag-NP was below the weight ratio of 15/85 (Ag-NP to NSP), and the detached Ag-NP from the Ag-NP/NSP (30/70) and Ag-NP/SMA hybrids were observed by TEM. Ames test was performed to assess the mutagenic potential of different compositions of Ag-NP/NSP, only Ag-NP/NSP (30/70) and Ag-NP/SMA hybrids exhibited mutagenicity when the concentration was 1.09 ppm or higher. In viewing of cytotoxicity using MTT tests toward HaCaT cells, the IC30 of Ag-NP/NSP (1/99, 7/93 and 15/85) were 1416.7, 243.6, and 148.9 ppm respectively, while Ag-NP/SMA was 64.8 ppm. The IC30 of Ag-NP/NSP (1/99, 7/93 and 15/85) were at least 833, 78 and 7 folds higher than their corresponding minimum inhibitory concentrations (MIC) respectively, and whereas Ag-NP/SMA was 6.4 folds. The Ag-NP/NSP and Ag-NP/SMA hybrids had been further investigated for genotoxicity by chromosomal aberrations and in vivo micronucleus assay within the concentration at IC10 and IC30, only Ag-NP/SMA showed a higher frequency of chromosomal aberrations. Our findings indicated that the viability of utilizing the NSP to maintain Ag-NP for antimicrobial activity, and the high-surface area of NSP served as an excellent support for associating Ag-NP and consequently rendering the mitigation of the inherent toxicity of Ag-NP in clinical uses.

scholarly journals The Mitigating Effect of Jatropha curcas L. Latex against Genotoxicity Induced by Doxorubicin

2019 ◽  
pp. 1-9
Author(s):  
Elisa Flávia Luiz Cardoso Bailão ◽  
Illana Reis Pereira ◽  
Jeniffer Gabrielle Vieira Silva ◽  
Maria Alice Montes de Sousa ◽  
Fábio Santos Matos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Drug Interactions ◽  
Jatropha Curcas ◽  
Mammalian Cells ◽  
Biodiesel Production ◽  
Mouse Bone Marrow ◽  
Mutagenic Potential ◽  
Medicinal Uses ◽  
Toxicity Response

Jatropha curcas (Euphorbiaceae) is a multiple purpose lacticiferous plant with potential for biodiesel production and medicinal uses. There is in the literature different analyses about the toxic and cytogenotoxic effects of J. curcas extracts, but few information about latex toxicity. In addition, few models were employed to evaluate the toxicity response to J. curcas latex, and the toxicity in in vivo mammal’s model has not been tested yet. The cytotoxic, mutagenic and antimutagenic potential of J. curcas latex were investigated using mouse bone marrow erythrocytes. The results indicated a cytotoxic and mutagenic potential of this latex to mammalian cells. But, when J. curcas latex was co-administrated with doxorubicin (DXR – chemotherapy medication), a reduction in the number of micronuclei was observed, indicating an interaction between J. curcas latex and DXR. The interaction of latex with DXR can cause a reduction in the activity of this drug and impair the treatment of its users. Moreover, there is a lack of data on herb–drug interactions, what should be more investigated to safeguard the wellbeing of patients.

Vacuoles Induced in Mammalian Cells by Helicobacter Cytotoxin are Acidic Organelles

1990 ◽  
Vol 48 (3) ◽  
pp. 168-169
Author(s):  
M. H. Chestnut ◽  
C. E. Catrenich
Keyword(s):  
Acridine Orange ◽  
Mammalian Cells ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Ulcer Disease ◽  
Gastroduodenal Disease ◽  
H Pylori

Helicobacter pylori is a non-invasive, Gram-negative spiral bacterium first identified in 1983, and subsequently implicated in the pathogenesis of gastroduodenal disease including gastritis and peptic ulcer disease. Cytotoxic activity, manifested by intracytoplasmic vacuolation of mammalian cells in vitro, was identified in 55% of H. pylori strains examined. The vacuoles increase in number and size during extended incubation, resulting in vacuolar and cellular degeneration after 24 h to 48 h. Vacuolation of gastric epithelial cells is also observed in vivo during infection by H. pylori. A high molecular weight, heat labile protein is believed to be responsible for vacuolation and to significantly contribute to the development of gastroduodenal disease in humans. The mechanism by which the cytotoxin exerts its effect is unknown, as is the intracellular origin of the vacuolar membrane and contents. Acridine orange is a membrane-permeant weak base that initially accumulates in low-pH compartments. We have used acridine orange accumulation in conjunction with confocal laser scanning microscopy of toxin-treated cells to begin probing the nature and origin of these vacuoles.

Cytological changes induced by platinum-thymine in sarcoma-180 cells: Electron microscopy study

1990 ◽  
Vol 48 (3) ◽  
pp. 290-291
Author(s):  
Gustav Ofosu
Keyword(s):  
Mammalian Cells ◽  
Antitumor Agent ◽  
Microscopy Study ◽  
Electron Microscopy Study ◽  
Limiting Factor ◽  
Sarcoma 180 ◽  
Electron Microscopic ◽  
Cytological Changes

Platinum-thymine has been found to be a potent antitumor agent, which is quite soluble in water, and lack nephrotoxicity as the dose-limiting factor. The drug has been shown to interact with DNA and inhibits DNA, RNA and protein synthesis in mammalian cells in vitro. This investigation was undertaken to elucidate the cytotoxic effects of piatinum-thymine on sarcoma-180 cells in vitro ultrastructurally, Sarcoma-180 tumor bearing mice were treated with intraperitoneal injection of platinum-thymine 40mg/kg. A concentration of 60μg/ml dose of platinum-thymine was used in in vitro experiments. Treatments were at varying time intervals of 3, 7 and 21 days for in vivo experiments, and 30, 60 and 120 min., 6, 12, and 24th in vitro. Controls were not treated with platinum-thymine.Electron microscopic analyses of the treated cells in vivo and in vitro showed drastic cytotoxic effect.

Sign in / Sign up

Export Citation Format

Share Document