Synthesis and biological activity of 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F06%3A00002646" target="_blank" >RIV/61989592:15310/06:00002646 - isvavai.cz</a>

Alternative codes found

RIV/61389030:_____/06:00082517

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Synthesis and biological activity of 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin

Original language description

The trisubstituted purine myoseverin has been recently identified as a novel inhibitor of microtubule assembly. To analyze the effects of modifying its heterocyclic skeleton, we prepared 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin and compared their biological activities. Rearrangement of nitrogen atoms in the heterocycle changes the affinity of the compounds to purified tubulin, as demonstrated by the results of polymerization assays, and affects the proliferation of cancer cell lines. Surprisingly, compound E2GG, a pyrazolo[4,3-d]pyrimidine analogue of myoseverin, displayed inhibitory activity towards both tubulin polymerization and the activity of cyclin-dependent kinases 1, 2 and 7. Such a dual specificity-inhibitor offers a starting point for developing a novel class of antiproliferative agents.

Czech name

Synthesis and biological activity of 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin

Czech description

The trisubstituted purine myoseverin has been recently identified as a novel inhibitor of microtubule assembly. To analyze the effects of modifying its heterocyclic skeleton, we prepared 8-azapurine and pyrazolo[4,3-d]pyrimidine analogues of myoseverin and compared their biological activities. Rearrangement of nitrogen atoms in the heterocycle changes the affinity of the compounds to purified tubulin, as demonstrated by the results of polymerization assays, and affects the proliferation of cancer cell lines. Surprisingly, compound E2GG, a pyrazolo[4,3-d]pyrimidine analogue of myoseverin, displayed inhibitory activity towards both tubulin polymerization and the activity of cyclin-dependent kinases 1, 2 and 7. Such a dual specificity-inhibitor offers a starting point for developing a novel class of antiproliferative agents.

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

Z - Vyzkumny zamer (s odkazem do CEZ)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2006

Confidentiality

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

Name of the periodical

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

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Volume of the periodical

41

Issue of the periodical within the volume

12

Country of publishing house

FR - FRANCE

Number of pages

7

Pages from-to

1405-1411

UT code for WoS article

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EID of the result in the Scopus database

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