In silico and in vitro comparative activity of novel experimental derivatives against Leishmania major and Leishmania infantum promastigotes

Khademvatan, Shahram; Adibpour, Neda; Eskandari, Alborz; Rezaee, Saeed; Hashemitabar, Mahmoud; Rahim, Fakher

doi:10.1016/j.exppara.2013.07.004

Cited by 23 publications

(19 citation statements)

References 47 publications

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“…Therefore, bioinformatics, can be used to revisit different drug compounds to be administered against VL (25). Khademvatan et al showed, in silico and in vitro study could lead to find potential drugs against leishmaniasis (10).…”

Section: Discussionmentioning

confidence: 99%

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Study of Ethinyl Estradiol Activity Against Promastigotes, Axenic and Macrophage-Dwelling Amastigotes of Leishmania infantum by Using Atomic Force Microscopy and Methyl Thiazolyl Tetrazolium Methods

Shadnoush

Arjmand

Rahim

et al. 2019

Jundishapur J Microbiol

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Background: In the era of drug resistant organisms, there exists a huge need to overcome this issue. Drug repositioning is the action of repurposing current drugs against alternative targets. Objectives: Herein, we assessed the antileishmanial activity of ethinyl estradiol and tolmetin on the promastigotes and amastigotes of Leishmania infantum, using methyl thiazolyl tetrazolium (MTT) and atomic force microscopy (AFM) methods. Methods: Following previous in silico evaluation of 3358 FDA-approved compounds, ethinyl estradiol and tolmetin drugs were selected. Promastigote assay was done in RPMI 1640 culture in 96-well plates (10 5 /100 µL). Also, axenic amastigotes cultured in acidic RPMI 1640 were seeded in 96-well plates (5 × 10 4 parasites). Raw 264.7 macrophages were seeded at a density of 3 × 10 6 cells/well. Then, the macrophages were infected with metacyclic promastigotes of L. infantum. Also, drug solvent and amphotericin B were considered as control wells. Drug challenge was performed in triplicate with different concentrations of ethinyl estradiol (250, 125, 62.5, 31.25, 15.62 and 7.81 µg/mL) and tolmetin (200, 100, 50, 25, 12.5 and 6.25 µg/mL) and cell viability was assessed by MTT assay. AFM imaging was done to observe morphological changes. Results: The main finding of our investigation was the substantial effect of ethinyl estradiol on promastigotes, and amastigotes of L. infantum during 24, 48 and 72 h, according to MTT results and cellular morphology observations. Thus, the IC50 of this drug on promastigote, axenic amastigotes and macrophage-dwelling amastigotes during 72 h was 23, 45 and 32 µg/mL, respectively. However, tolmetin was not effective against L. infantum parasites. Cellular alteration, was observed by AFM technique. Conclusions: This study showed that ethinyl estradiol had good anti-leishmanial activity and it is recommended to test this drug under in vivo condition. With the aid of drug repurposing we could substitute the old drugs with novel compounds for a specific disease.

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Section: Discussionmentioning

confidence: 99%

“…Several risk factors such as travel to endemic areas, decreased immunity, absence of an efficient vaccine enhance the occurrence of leishmaniasis (10). The primary medication for leishmaniasis mostly relies on Glucantime and Pentostam (first-line therapies) as well as Pentamidine and amphotericin B (second-line therapies).…”

Section: Introductionmentioning

confidence: 99%

Study of Ethinyl Estradiol Activity Against Promastigotes, Axenic and Macrophage-Dwelling Amastigotes of Leishmania infantum by Using Atomic Force Microscopy and Methyl Thiazolyl Tetrazolium Methods

Shadnoush

Arjmand

Rahim

et al. 2019

Jundishapur J Microbiol

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“…91,92 This method is a first step in structure based and rational drug design and is sometimes referred to as computer-aided drug design. Through in silico techniques, a specific drug is evaluated prior to design by various model building patterns such as QSAR or density functional theory.…”

Section: Ln Silico and Computer Based Modeling For Treatment And Respmentioning

confidence: 99%

Genetics and epigenetics of myelodysplastic syndromes and response to drug therapy: new insights

Shahrabi¹,

Khosravi²,

Shahjahani³

et al. 2016

Oncol Rev

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Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic neoplasms ocurring mostly in the elderly. The clinical outcome of MDS patients is still poor despite progress in treatment approaches. About 90% of patients harbor at least one somatic mutation. This review aimed to assess the potential of molecular abnormalities in understanding pathogenesis, prognosis, diagnosis and in guiding choice of proper therapy in MDS patients. Papers related to this topic from 2000 to 2016 in PubMed and Scopus databases were searched and studied. The most common molecular abnormalities were TET2, ASXL1 as well as molecules involved in spliceosome machinery (U2AF1, SRSF2 and SF3B1). Patients with defects in TET2 molecule show better response to treatment with azacitidine. IDH and DNMT3A mutations are associated with a good response to decitabine therapy. In addition, patients with del5q subtype harboring TP53 mutation do not show a good response to lenalidomide therapy.In general, the results of this study show that molecular abnormalities can be associated with the occurrence of a specific morphological phenotype in patients. Therefore, considering the morphology of patients, different gene profiling methods can be selected to choice the most appropriate therapeutic measure in these patients in addition to faster and more cost-effective diagnosis of molecular abnormalities.

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“…Cutaneous leishmaniasis is most highlighted in 10 nations including Columbia, Brazil, Costa Rica, Peru, Iran, Syria, Afghanistan, Algeria, Ethiopia, and North Sudan (2). A number of risk factors such as migration to endemic ar-eas, urbanization with the increased risk of vector localization and man-made manipulation in the environment are involved in the occurrence and distribution of cutaneous leishmaniasis (4). Countries located in the Eastern Mediterranean territory such as Iran possess appropriate conditions for cutaneous leishmaniasis endemicity (5).…”

Section: Introductionmentioning

confidence: 99%

Genotyping of Causative Agents of Cutaneous Leishmaniasis in Patients Using PCR-RFLP Method in Dasht-e-Azadegan County, Southwest of Iran, in 2016

Khazael

Saki

Arjmand

2019

Jundishapur J Microbiol

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Background: As a neglected disease, cutaneous leishmaniasis renders considerable incidence rates. Eastern Mediterranean countries such as Iran are endemic for this infection. Objectives: Herein, we determined the species/strains of the causative agents of cutaneous leishmaniasis in Dasht-e-Azadegan, Khuzestan, Iran, using PCR-RFLP in 2016. Methods: We microscopically examined 80 smear slides from suspected patients referring to health centers of the city. After DNA extraction from slide materials, the amplification of the ITS1 fragment was done using the LITSR and L5.8S primer pair for Leishmania molecular detection. Subsequently, HaeIII (species level), TaqI (strain level), DpnI, and HpaII (mutation analysis) digestion was exerted based on the RFLP method. Results: Microscopic examination revealed the amastigote forms of Leishmania in all 80 samples. A 350 bp band was amplified by ITS1-PCR, which confirmed the infection at the molecular level. Following HaeIII digestion, 150 and 200 bp fragments were produced indicating Leishmania major. Also, TaqI digestion rendered 130 and 200 bp bands suggesting the A1 strain. Moreover, no mutations were detected in the genome of the identified L. major A1 strains by DpnI (140 and 200 bp bands) and HpaII (no digestion) digestion. Conclusions: The genotypic heterogeneity of Leishmania species is of utmost importance for better treatment choices, appropriate diagnosis, and preventive measures. Future work in the area should address the parasite strains in alternative vector/reservoir hosts.

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In silico and in vitro comparative activity of novel experimental derivatives against Leishmania major and Leishmania infantum promastigotes

Cited by 23 publications

References 47 publications

Study of Ethinyl Estradiol Activity Against Promastigotes, Axenic and Macrophage-Dwelling Amastigotes of Leishmania infantum by Using Atomic Force Microscopy and Methyl Thiazolyl Tetrazolium Methods

Study of Ethinyl Estradiol Activity Against Promastigotes, Axenic and Macrophage-Dwelling Amastigotes of Leishmania infantum by Using Atomic Force Microscopy and Methyl Thiazolyl Tetrazolium Methods

Genetics and epigenetics of myelodysplastic syndromes and response to drug therapy: new insights

Genotyping of Causative Agents of Cutaneous Leishmaniasis in Patients Using PCR-RFLP Method in Dasht-e-Azadegan County, Southwest of Iran, in 2016

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