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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA15-22194S" target="_blank" >GA15-22194S: Úloha GIT-PIX signálního komplexu při regulaci nukleace mikrotubulů žírných buněk</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Canadian Journal of Chemistry

ISSN

0008-4042

e-ISSN

—

Svazek periodika

95

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

CA - Kanada

Počet stran výsledku

7

Strana od-do

649-655

Kód UT WoS článku

000402316800003

EID výsledku v databázi Scopus

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