Interference Potential of Tannins and Chlorophylls in Zebrafish Phenotypic-Based Assays
| Autor: | Kazuhide S. Okuda, Pei Jean Tan, Nur Faizah Ruslan, Norazwana Samat, Mei Fong Ng, Vyomesh Patel |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Chlorophyll
0301 basic medicine animal structures Drug Evaluation Preclinical Angiogenesis Inhibitors Context (language use) 03 medical and health sciences 0302 clinical medicine In vivo Drug Discovery Sunitinib Animals Tannin Zebrafish chemistry.chemical_classification biology Drug discovery Diphenylamine Sunitinib malate biology.organism_classification Phenotype 030104 developmental biology Biochemistry chemistry 030220 oncology & carcinogenesis Benzamides embryonic structures Toxicity Molecular Medicine Tannins |
| Zdroj: | ASSAY and Drug Development Technologies. 16:408-419 |
| ISSN: | 1557-8127 1540-658X |
| DOI: | 10.1089/adt.2017.833 |
| Popis: | Natural products are prolific producers of diverse chemical scaffolds, which have yielded several clinically useful drugs. However, the complex features of natural products present challenges for identifying bioactive molecules using high-throughput screens. For most assays, measured endpoints are either colorimetric or luminescence based. Thus, the presence of the major metabolites, tannins, and chlorophylls, in natural products could potentially interfere with these measurements to give either false-positive or false-negative hits. In this context, zebrafish phenotypic assays provide an alternative approach to bioprospect naturally occurring bioactive compounds. Whether tannins and/or chlorophylls interfere in zebrafish phenotypic assays, is unclear. In this study, we evaluated the interference potential of tannins and chlorophylls against efficacy of known small-molecule inhibitors that are known to cause phenotypic abnormalities in developing zebrafish embryos. First, we fractionated tannin-enriched fraction (TEF) and chlorophyll-enriched fraction (CEF) from Camellia sinensis and cotreated them with PD0325901 [mitogen-activated protein kinase-kinase (MEK) inhibitor] and sunitinib malate (SM; anti-[lymph]angiogenic drug). While TEF and CEF did not interfere with phenotypic or molecular endpoints of PD0325901, TEF at 100 μg/mL partially masked the antiangiogenic effect of SM. On the other hand, CEF (100 μg/mL) was toxic when treated up to 6 dpf. Furthermore, CEF at 100 μg/mL potentially enhanced the activity of γ-secretase inhibitors, resulting in toxicity of treated embryos. Our study provides evidence that the presence of tannin and/or chlorophyll in natural products do interfere with zebrafish phenotype assays used for identifying potential hits. However, this may be target/assay dependent and thus requiring additional optimization steps to assess interference potential of tannins and chlorophylls before performing any screening assay. |
| Databáze: | OpenAIRE |
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