In vivo evaluation of indolyl glyoxamides in the phenotypic sea urchin embryo assay.
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.
Semenova
Marina N
MN
Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov Str, 119334 Moscow, Russia. ms@chemical-block.com
Kiselyov
Alex S
AS
Titov
Ilia Y
IY
Raihstat
Mikhail M
MM
Molodtsov
Maxim
M
Grishchuk
Ekaterina
E
Spiridonov
Ilia
I
Semenov
Victor V
VV
D000081:Acetamides / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D036703:Blastula / Q000378:metabolism*; D002417:Cattle; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D008954:Models, Biological; D047328:Paracentrotus / Q000166:cytology / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology*
D000081:Acetamides; D007211:Indoles; D014404:Tubulin; D050257:Tubulin Modulators; C419187:indibulin