Target-based vs. phenotypic screenings in Leishmania drug discovery: A marriage of convenience or a dialogue of the deaf?
| Autor: | Rosa M. Reguera, Rafael Balaña-Fouce, Estefanía Calvo-Álvarez, Raquel Álvarez-Velilla |
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| Jazyk: | angličtina |
| Předmět: |
In silico
Computational biology Biology Bioinformatics lcsh:Infectious and parasitic diseases Target HTS Pharmacology (medical) lcsh:RC109-216 HTS high throughput screening ComputingMethodologies_COMPUTERGRAPHICS Pharmacology Leishmania Drug discovery HCS High Content Screening NTD Neglected Tropical Diseases biology.organism_classification Phenotype Genetically modified organism Phenotypic HTS Infectious Diseases TDR Special Programme for Research and Training in Tropical Diseases Invited Article Neglected tropical diseases Parasitology |
| Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance, Vol 4, Iss 3, Pp 355-357 (2014) International Journal for Parasitology: Drugs and Drug Resistance |
| ISSN: | 2211-3207 |
| DOI: | 10.1016/j.ijpddr.2014.05.001 |
| Popis: | Graphical abstract Highlights • Target-based vs. target-free screenings are on the pipeline of drug discovery. • High Content Screenings have greater acceptance for drug discovery studies. • In vivo imaging of transgenic parasites are suitable for pre-clinical trials. Drug discovery programs sponsored by public or private initiatives pursue the same ambitious goal: a crushing defeat of major Neglected Tropical Diseases (NTDs) during this decade. Both target-based and target-free screenings have pros and cons when it comes to finding potential small-molecule leads among chemical libraries consisting of myriads of compounds. Within the target-based strategy, crystals of pathogen recombinant-proteins are being used to obtain three-dimensional (3D) structures in silico for the discovery of structure-based inhibitors. On the other hand, genetically modified parasites expressing easily detectable reporters are in the pipeline of target-free (phenotypic) screenings. Furthermore, lead compounds can be scaled up to in vivo preclinical trials using rodent models of infection monitoring parasite loads by means of cutting-edge bioimaging devices. As such, those preferred are fluorescent and bioluminescent readouts due to their reproducibility and rapidity, which reduces the number of animals used in the trials and allows for an earlier stage detection of the infective process as compared with classical methods. In this review, we focus on the current differences between target-based and phenotypic screenings in Leishmania, as an approach that leads to the discovery of new potential drugs against leishmaniasis. |
| Databáze: | OpenAIRE |
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