Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis

2008 ◽  
Vol 94 (3) ◽  
pp. 743-749 ◽  
Author(s):  
Alexa C. Rosypal ◽  
Karl A. Werbovetz ◽  
Manar Salem ◽  
Chad E. Stephens ◽  
Arvind Kumar ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Leishmania Tropica ◽  
In Vitro Growth ◽  
Old World ◽  
Causative Agents

Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis

2008 ◽  
Vol 94 (3) ◽  
pp. 743 ◽  
Author(s):  
Alexa C. Rosypal ◽  
Karl A. Werbovetz ◽  
Manar Salem ◽  
Chad E. Stephens ◽  
Arvind Kumar ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Leishmania Tropica ◽  
In Vitro Growth ◽  
Old World ◽  
Causative Agents

scholarly journals Use of Oral Miltefosine for Cutaneous Leishmaniasis in Canadian Soldiers Returning from Afghanistan

2008 ◽  
Vol 19 (6) ◽  
pp. 394-396 ◽  
Author(s):  
Yoav Keynan ◽  
Oscar E Larios ◽  
Marni C Wiseman ◽  
Marie Plourde ◽  
Marc Ouellette ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Middle Eastern ◽  
Parasitic Infections ◽  
Leishmania Tropica ◽  
Old World ◽  
Fluconazole Therapy

Old world cutaneous leishmaniasis (CL) is caused byLeishmania majorandLeishmania tropica,and is endemic to several Asian and Middle-Eastern countries where the rates of infection can be substantial. CL is one of the most common vector-transmitted parasitic infections in Afghanistan. Six cases of CL in Canadian soldiers returning from Afghanistan are reported in the present study. Their lesions did not improve with fluconazole therapy, and the organism demonstrated in vitro resistance. Oral miltefosine seemed effective.

scholarly journals EAPB0503: an imiquimod analog with potent in vitro activity against cutaneous leishmaniasis caused by Leishmania major and Leishmania tropica

2020 ◽  
Vol 13 (12) ◽  
pp. 2112
Author(s):  
Rana El Hajj ◽  
Hanady Bou Youness ◽  
Laurence Lachaud ◽  
Patrick Bastien ◽  
Carine Masquefa ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Vitro Activity ◽  
Leishmania Tropica ◽  
In Vitro Activity

scholarly journals EAPB0503: An Imiquimod analog with potent in vitro activity against cutaneous leishmaniasis caused by Leishmania major and Leishmania tropica

2018 ◽  
Vol 12 (11) ◽  
pp. e0006854 ◽  
Author(s):  
Rana El Hajj ◽  
Hanady Bou Youness ◽  
Laurence Lachaud ◽  
Patrick Bastien ◽  
Carine Masquefa ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Vitro Activity ◽  
Leishmania Tropica ◽  
In Vitro Activity

Leishmanicidal Activity of Plant Extracts from Sefrou, a Moroccan Focus of Leishmaniasis, against Various Leishmania Parasites in the Promastigote Stage

2018 ◽  
Vol 17 (2) ◽  
pp. 83-89 ◽  
Author(s):  
I. Zeouk ◽  
A. Et-Touys ◽  
M. Balouiri ◽  
H. Fellah ◽  
A. El Ouali Lalami ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Plant Extracts ◽  
Leishmania Infantum ◽  
Leishmania Major ◽  
Local Population ◽  
Public Health Problem ◽  
World Health ◽  
Total Phenolic ◽  
Leishmania Tropica ◽  
Cistus Salviifolius

According to the World Health Organization, leishmaniasis remains a major worldwide public health problem. The province of Sefrou located in the center of Morocco is a focus of cutaneous leishmaniasis. The present study aims at evaluating the antileishmanial potential of Berberis sp.,Crataegus oxyacantha, Cistus salviifolius, Ephedra altissima and Lavandula dentatafrequently used by the local population. Methanolic extracts were tested against the promastigote form ofLeishmania tropica, Leishmania majorandLeishmania infantumusing tetrazolium-based colorimetric (MTT) assay. The total phenol and flavonoids content of all extracts were determined using the Folin–Ciocalteu reagent, aluminum chloride, and potassium acetate solutions respectively. The plant extracts exhibited antileishmanial activity with variability depending on the tested strain and the plant species compared to Glucantime® used as control (IC50 (the half maximal inhibitory concentration) > 1,000 μg/mL). The best inhibition was observed with Berberis sp., againstLeishmania major(IC50 = 394.40 ± 3.02 μg/ml), andEphedra altissima(reported for the first time) againstLeishmania infantum(IC50 = 490.84 ± 3.15 μg/mL).Leishmania tropicahas shown the same sensitivity behavior toward the five extracts (in average IC50 = 540 ± 11.20 μg/mL). The total phenolic content was higher forCrataegus oxyacanthaandCistus salviifolius(140.67 ± 3.17 μg eq Gallic Acid (GA)/ mg of Extract (E) and 133.83 ± 9.03 μg eq GA/mg of E respectively), while flavonoid was higher forCistus salviifoliusandLavandula dentata(57.92 ± 2.46 μg eq Quercetin (Que)/ mg of Extract (E) and 41.53 ± 1.74 μg eq Que/mg of E). All the tested extracts present some promising aspects that may cure cutaneous leishmaniasis in the center of Morocco; further bioguided assays are needed to isolate the fractions and the bioactive molecule.

Evaluating the Effect of Cinnarizine on Promastigotes and Amastigotes forms of Leishmania major

2020 ◽  
Vol 20 (4) ◽  
pp. 550-555 ◽  
Author(s):  
Lima Asgharpour Sarouey ◽  
Parvaneh Rahimi-Moghaddam ◽  
Fatemeh Tabatabaie ◽  
Khadijeh Khanaliha
Keyword(s):  
Flow Cytometry ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Inhibitory Effect ◽  
Control Group ◽  
Secondary Infections ◽  
Ic50 Values ◽  
J774 Cells ◽  
Mtt Assays

: As an important global disease, cutaneous leishmaniasis is associated with complications such as secondary infections and atrophic scars. The first line treatment with antimonials is expensive and reported to have serious side effects and enhance resistance development. The main objective of this study was to evaluate the effect of Cinnarizine on standard strains of Leishmania major because of paucity of information on this subject. Methods: In this experimental study, four concentrations of the drug (5, 10, 15 and 20 μg/ml) were added to Leishmania major cultures at 24, 48 and 72 hours intervals. MTT assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) was ascertained by counting parasites. The inhibitory effect of the drug was compared with that of Glucantime. Flow-cytometry was performed to investigate apoptosis. Each test was repeated thrice. Results: The IC50 values of Cinnarizine after 72 hours were calculated to be 34.76 μg/ml and 23.73 μg/ml for promastigotes and amastigotes, respectively. The results of MTT assays showed 48 % promastigote viability after 72 hour-exposure to Cinnarizine at 20 μg/ml concentration. Programmed cell death in promastigote- and amastigote-infected macrophages was quantified to be 13.66 % and 98.7 %, respectively. Flow- cytometry analysis indicated that Cinnarizine induced early and late apoptosis in parasites. All treatments produced results which differed significantly from control group (P<0.05). Conclusion: Cinnarizine showed low toxicity with anti-leishmanial and apoptosis effects on both promastigote and intracellular amastigote forms. Therefore, we may suggest further assessment on animal models of this drug as candidates for cutaneous leishmaniasis therapy.

scholarly journals Novel Compounds Active against Leishmania major

2006 ◽  
Vol 50 (2) ◽  
pp. 474-479 ◽  
Author(s):  
Stephanie St. George ◽  
Jeanette V. Bishop ◽  
Richard G. Titus ◽  
Claude P. Selitrennikoff
Keyword(s):  
Side Effects ◽  
Drug Development ◽  
Leishmania Major ◽  
Murine Macrophage ◽  
Sodium Stibogluconate ◽  
Chemical Library ◽  
Old World ◽  
Serious Disease ◽  
Unique Chemical

ABSTRACT Leishmania major is an important trypanosomatid pathogen that causes leishmaniasis, which is a serious disease in much of the Old World. Current treatments include a small number of antimony compounds that, while somewhat effective, are limited by serious side effects. We have screened a small portion of a unique chemical library and have found at least three novel compounds that are effective against L. tarentolae and L. major in vitro and in a murine macrophage model of L. major infection. These compounds were effective in both assays at doses significantly lower than those of sodium stibogluconate (Pentostam) and represent possible candidates for drug development.

scholarly journals Pharmacokinetics of Miltefosine in Old World Cutaneous Leishmaniasis Patients

2008 ◽  
Vol 52 (8) ◽  
pp. 2855-2860 ◽  
Author(s):  
Thomas P. C. Dorlo ◽  
Pieter P. A. M. van Thiel ◽  
Alwin D. R. Huitema ◽  
Ron J. Keizer ◽  
Henry J. C. de Vries ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Half Life ◽  
Leishmania Major ◽  
The Body ◽  
Population Pharmacokinetic ◽  
Mixed Effect ◽  
Old World ◽  
Elimination Half Life ◽  
Elimination Half ◽  
End Of Treatment

ABSTRACT The pharmacokinetics of miltefosine in leishmaniasis patients are, to a great extent, unknown. We examined and characterized the pharmacokinetics of miltefosine in a group of patients with Old World (Leishmania major) cutaneous leishmaniasis. Miltefosine plasma concentrations were determined in samples taken during and up to 5 months after the end of treatment from 31 Dutch military personnel who contracted cutaneous leishmaniasis in Afghanistan and were treated with 150 mg miltefosine/day for 28 days. Samples were analyzed with a validated liquid chromatography-tandem mass spectrometry assay with a lower limit of quantification (LLOQ) of 4 ng/ml. Population pharmacokinetic modeling was performed with nonlinear mixed-effect modeling, using NONMEM. The pharmacokinetics of miltefosine could best be described by an open two-compartment disposition model, with a first elimination half-life of 7.05 days and a terminal elimination half-life of 30.9 days. The median concentration in the last week of treatment (days 22 to 28) was 30,800 ng/ml. The maximum duration of follow-up was 202 days after the start of treatment. All analyzed samples contained a concentration above the LLOQ. Miltefosine is eliminated from the body much slower than previously thought and is therefore still detectable in human plasma samples taken 5 to 6 months after the end of treatment. The presence of subtherapeutic miltefosine concentrations in the blood beyond 5 months after treatment might contribute to the selection of resistant parasites, and moreover, the measures for preventing the teratogenic risks of miltefosine treatment should be reconsidered.

scholarly journals Zinc(II)-Dipicolylamine Coordination Complexes as Targeting and Chemotherapeutic Agents for Leishmania major

2016 ◽  
Vol 60 (5) ◽  
pp. 2932-2940 ◽  
Author(s):  
Douglas R. Rice ◽  
Paola Vacchina ◽  
Brianna Norris-Mullins ◽  
Miguel A. Morales ◽  
Bradley D. Smith
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Mammalian Cells ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Coordination Complexes ◽  
Chemotherapeutic Agents ◽  
Selective Toxicity ◽  
Content Type

ABSTRACTCutaneous leishmaniasis is a neglected tropical disease that causes painful lesions and severe disfigurement. Modern treatment relies on a few chemotherapeutics with serious limitations, and there is a need for more effective alternatives. This study describes the selective targeting of zinc(II)-dipicolylamine (ZnDPA) coordination complexes towardLeishmania major, one of the species responsible for cutaneous leishmaniasis. Fluorescence microscopy ofL. majorpromastigotes treated with a fluorescently labeled ZnDPA probe indicated rapid accumulation of the probe within the axenic promastigote cytosol. The antileishmanial activities of eight ZnDPA complexes were measured using anin vitroassay. All tested complexes exhibited selective toxicity againstL. majoraxenic promastigotes, with 50% effective concentration values in the range of 12.7 to 0.3 μM. Similar toxicity was observed against intracellular amastigotes, but there was almost no effect on the viability of mammalian cells, including mouse peritoneal macrophages.In vivotreatment efficacy studies used fluorescence imaging to noninvasively monitor changes in the red fluorescence produced by an infection of mCherry-L. majorin a mouse model. A ZnDPA treatment regimen reduced the parasite burden nearly as well as the reference care agent, potassium antimony(III) tartrate, and with less necrosis in the local host tissue. The results demonstrate that ZnDPA coordination complexes are a promising new class of antileishmanial agents with potential for clinical translation.

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