| Autor: |
Dantas RF; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica Experimental de Computacional de Fármacos, Rio de Janeiro, RJ, Brasil., Torres-Santos EC; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanosomatídeos, Rio de Janeiro, RJ, Brasil., Silva FP Jr; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica Experimental de Computacional de Fármacos, Rio de Janeiro, RJ, Brasil. |
| Jazyk: |
angličtina |
| Zdroj: |
Memorias do Instituto Oswaldo Cruz [Mem Inst Oswaldo Cruz] 2022 Mar 11; Vol. 117, pp. e210402. Date of Electronic Publication: 2022 Mar 11 (Print Publication: 2022). |
| DOI: |
10.1590/0074-02760210402 |
| Abstrakt: |
Diseases caused by trypanosomatid parasites affect millions of people mainly living in developing countries. Novel drugs are highly needed since there are no vaccines and available treatment has several limitations, such as resistance, low efficacy, and high toxicity. The drug discovery process is often analogous to finding a needle in the haystack. In the last decades a so-called rational drug design paradigm, heavily dependent on computational approaches, has promised to deliver new drugs in a more cost-effective way. Paradoxically however, the mainstay of these computational methods is data-driven, meaning they need activity data for new compounds to be generated and available in databases. Therefore, high-throughput screening (HTS) of compounds still is a much-needed exercise in drug discovery to fuel other rational approaches. In trypanosomatids, due to the scarcity of validated molecular targets and biological complexity of these parasites, phenotypic screening has become an essential tool for the discovery of new bioactive compounds. In this article we discuss the perspectives of phenotypic HTS for trypanosomatid drug discovery with emphasis on the role of image-based, high-content methods. We also propose an ideal cascade of assays for the identification of new drug candidates for clinical development using leishmaniasis as an example. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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