Synthesis and biological evaluation of structurally simplified noscapine analogues as microtubule binding agents

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00483728" target="_blank" >RIV/68378050:_____/17:00483728 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1139/cjc-2016-0649" target="_blank" >http://dx.doi.org/10.1139/cjc-2016-0649</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1139/cjc-2016-0649" target="_blank" >10.1139/cjc-2016-0649</a>

Result language
angličtina
Original language name
Synthesis and biological evaluation of structurally simplified noscapine analogues as microtubule binding agents
Original language description
This paper reports on the results of chemical synthesis and biological assays performed on several new analogues of noscapine. We have successfully synthesized four noscapine analogues called 1a-4a, as well as their four corresponding enantiomers called 1b-4b. The chemical pathway consisted of three steps with yields in excess of 60% in each step. Subsequently, we have performed biological activity assays intended to reveal the mode of action of these compounds on microtubules in buffer and in cancer cell lines. We have assayed fluorescence quenching effects in microtubule polymerization experiments, cytotoxicity evaluation in breast cancer cell lines, as well as microtubule dynamicity assessments, for each of the synthesized compounds. Finally, we performed computational docking simulations to two binding sites on beta-tubulin: (a) the colchicine binding site and (b) the noscapine binding site. Our results indicate that these compounds have relatively low cytotoxicity profile and less pronounced effects on microtubule dynamics compared with noscapine. Our computational results indicate that these compounds bind to both putative binding sites but have higher affinity for the colchicine site.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GA15-22194S" target="_blank" >GA15-22194S: Role of GIT-PIX signaling complex in regulation of microtubule nucleation in mast cells</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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