Leishmaniaamastigotes as targets for drug screening

Monte-Alegre, Adriano Figueiredo; Ouaissi, Ali; Sereno, Denis

doi:10.1186/1475-9292-5-6

Cited by 11 publications

(2 citation statements)

References 21 publications

(14 reference statements)

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“…In fact, in a previous study, in order to co-immunoprecipitate a sufficient quantity of interacting LiSIR2RP1 partner(s) for identification by mass spectrometry, we were compelled to use transfected parasites overexpressing Li-SIR2RP1. [34] Therefore, this might explain the discrepancies between the IC 50 values.…”

Section: Enzyme Inhibitionmentioning

confidence: 97%

Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Protein 1

et al. 2009

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The NAD(+)-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD(+)-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC(50) values in the single-digit micromolar range for the most potent compounds). Structure-activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC(50) values of 5.7 and 97.4 microM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD(+)-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.

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Section: Enzyme Inhibitionmentioning

confidence: 97%

Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Protein 1

et al. 2009

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“… 14 In the past few years, reporter gene technology has been developed to make drug screening more efficient by producing objective quantitative data, decreasing manual labor, and increasing throughput. 14 , 15 In addition, new high-content screens utilizing reporter proteins and fluorescent dyes have been established for conducting amastigote-macrophage dose–response and screen assays. 16 – 18 …”

Section: Introductionmentioning

confidence: 99%

Antileishmanial Activity of Compounds Derived from the Medicines for Malaria Venture Open Access Box Against Intracellular Leishmania major Amastigotes

Khraiwesh¹,

Leed²,

Roncal³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Leishmaniasis is a complex tropical disease caused by kinetoplastid parasitic protozoa of the genus Leishmania and is transmitted by the sand fly insect vector. Cutaneous leishmaniasis (CL) is the most common form of this disease, and CL infections often result in serious skin lesions and scars. CL remains a public health problem in many endemic countries worldwide because of the absence of effective, safe, and cost-effective drugs for treatment. One of the strategies we chose to use to find novel chemical entities worthy of further development as antileishmanials involved screening synthetic and natural products libraries. In our study, we developed a Leishmania major intracellular amastigote assay that uses the activity of luciferase as a measure of parasite proliferation and used this assay to screen a collection of 400 compounds obtained from Medicines for Malaria Venture (MMV) for their antileishmanial activity. Our results showed that 14 compounds identified by MMV as antimalarial drugs have antileishmanial activity and can potentially be optimized for CL drug development.

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Characterization of the Leishmanicidal Activity of Antimicrobial Peptides

Luque‐Ortega

Rivas

2009

Methods in Molecular Biology

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This chapter describes the basic methodology to assay the activity of antimicrobial peptides (AMPs) on Leishmania, a human protozoan parasite. The protocols included can be methodologically divided into two major blocks. The first one addresses the basic technology for growth of the different stages of Leishmania, assessment of leishmanicidal activity, and monitoring of plasma membrane permeabilization. The second block encompasses the monitoring of bioenergetic parameters of the parasite, visualization of structural damage by transmission electron microscopy, or those methods more closely related to the involvement of intracellular AMP targets, as subcellular localization of the peptide and induction of parasite apoptosis.

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Leishmaniaamastigotes as targets for drug screening

Cited by 11 publications

References 21 publications

Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Protein 1

Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Protein 1

Antileishmanial Activity of Compounds Derived from the Medicines for Malaria Venture Open Access Box Against Intracellular Leishmania major Amastigotes

Characterization of the Leishmanicidal Activity of Antimicrobial Peptides

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