A Novel Microtubule Destabilizing Entity from Orthogonal Synthesis of Triazine Library and Zebrafish Embryo Screening

Moon, Ho Sang; Jacobson, Eric S.; Khersonsky, Sonya M.; Luzung, Michael R.; Walsh, Daniel P.; Xiong, Wenhao; Lee, Jae Woo; Parikh, Puja B.; Lam, Jørgen; Kang, Tae Wook; Rosania, Gustavo R.; Schier, Alexander F.; Chang, Young‐Tae

doi:10.1021/ja026720i

Cited by 120 publications

(72 citation statements)

References 14 publications

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“…Over the last few years, phenotypebased developmental screens using wild-type zebrafish embryos have identified multiple compounds that cause general defects in embryogenesis and now await further characterization (Sternson et al, 2001;Moon et al, 2002;Spring et al, 2002;Wong et al, 2004). Chemical screens were also designed to identify novel bioactive compounds that affect the development of specific organs, physiological activities, or cellular processes in zebrafish (Table 2).…”

Section: The Spectrum Of Chemical Screens Performed In Zebrafishmentioning

confidence: 99%

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Wheeler

Brändli

2009

Developmental Dynamics

154

129

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Chemical genetics uses small molecules to modulate protein function and, in principle, has the potential to perturb any biochemical event in a complex cellular context. The application of chemical genetics to dissect biological processes has become an attractive alternative to mutagenesis screens due to its technical simplicity, inexpensive reagents, and low-startup costs. In vertebrates, only fish and amphibians are amenable to chemical genetic screens. Xenopus frogs share a long evolutionary history with mammals and so represent an excellent model to predict human biology. In this review, we discuss the lessons learned from chemical genetic studies carried out in zebrafish and Xenopus. We highlight how Xenopus can be employed as a convenient first-line animal model at various stages of the drug discovery and development process and comment on how they represent much-needed tools to bridge the gap between traditional in vitro and preclinical mammalian assays in biomedical research and drug development. Developmental

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Section: The Spectrum Of Chemical Screens Performed In Zebrafishmentioning

confidence: 99%

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Wheeler

Brändli

2009

Developmental Dynamics

154

129

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“…The zebrafish embryo is becoming an increasingly important model for studies in pharmacology (Parng et al, 2002) and vertebrate toxicology (Teraoka et al, 2003), as well as molecular biology (e.g., Malicki et al, 2002) and drug discovery (Moon et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades

Berry

Gantar

Gawley

et al. 2004

Comparative Biochemistry and Physiology Part C: Toxicology &

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The genus of filamentous cyanobacteria, Lyngbya, has been found to be a rich source of bioactive metabolites. However, identification of such compounds from Lyngbya has largely focused on a few marine representatives. Here, we report on the pharmacology and toxicology of pahayokolide A from a freshwater isolate, Lyngbya sp. strain 15−2, from the Florida Everglades. Specifically, we investigated inhibition of microbial representatives and mammalian cell lines, as well as toxicity of the compound to both invertebrate and vertebrate models. Pahayokolide A inhibited representatives of Bacillus, as well as the yeast, Saccharomyces cerevisiae. Interestingly, the compound also inhibited several representatives of green algae that were also isolated from the Everglades. Pahayokolide A was shown to inhibit a number of cancer cell lines over a range of concentrations (IC 50 varied from 2.13 to 44.57 μM) depending on the cell-type. When tested against brine shrimp, pahayokolide was only marginally toxic at the highest concentrations tested (1 mg/mL). The compound was, however, acutely toxic to zebrafish embryos (LC 50 =2.15 μM). Possible biomedical and environmental health aspects of the pahayokolides remain to be investigated; however, the identification of bioactive metabolites such as these demonstrates the potential of the Florida Everglades as source of new toxins and drugs.

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“…Poor therapeutic indexes and other unrecognized factors made the failure of these molecules [91]. Figure 18) is a microtubule destabilizing agent with potent growth inhibition against U936 cells (GI 50 = 1 μM) [140]. Tubulyzine ( Figure 18) is a trisubstituted 1, 3, 5-triazine derivative with potent microtubule disassembly properties [141].…”

Section: 3 5-triazine Derivatives As Microtubules Inhibitorsmentioning

confidence: 99%

A Systematic Review on Antitumor Agents with 1, 3, 5-triazines

Liu¹

2015

Med chem

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A Novel Microtubule Destabilizing Entity from Orthogonal Synthesis of Triazine Library and Zebrafish Embryo Screening

Abstract: The first orthogonal combinatorial synthesis of a high-purity triazine library was demonstrated. Novel triazine-based microtubule inhibitors were discovered by an efficient zebrafish embryo screening and in vitro microtubule polymerization assay.

Cited by 120 publications

References 14 publications

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades

A Systematic Review on Antitumor Agents with 1, 3, 5-triazines

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