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Research Article: In vivo Evaluation of Indolyl Glyoxamides in the Phenotypic Sea Urchin Embryo Assay
Author(s) -
Semenova Mari.,
Kiselyov Alex S.,
Titov Ilia Y.,
Raihstat Mikhail M.,
Molodtsov Maxim,
Grishchuk Ekaterina,
Spiridonov Ilia,
Semenov Victor V.
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00591.x
Subject(s) - sea urchin , in vivo , embryo , biology , in vitro , tubulin , microbiology and biotechnology , indole test , embryogenesis , microtubule , chemistry , biochemistry , genetics
We have devised a ‘one‐pot’ phenotypic in vivo assay for the rapid evaluation of potential tubulin inhibitors using the sea urchin embryo model. An effect of a small molecule on two specific developmental stages of sea urchin embryo, namely: (i) fertilized egg test for antimitotic activity and (ii) behavioral monitoring of a free‐swimming blastulae for changes in the embryo swimming pattern could be quantified by a threshold concentration resulting in respective abnormalities. Derivatives of the clinical candidate D‐24851 featured good correlation between activity in tubulin polymerization assay and our in vivo data. Importantly, we demonstrated that in these series, the N ‐substitution of indole is non‐essential to attain profound in vitro and cellular effects.