Synthesis and bioevaluation of new vascular-targeting and anti-angiogenic thieno[2,3-d]pyrimidin-4(3H)-ones

A series of forty-six 5,6-annulated 2-arylthieno [2,3-d]pyrimidin-4(3H)-ones were prepared as potentially pleiotropic anticancer drugs with variance in the tubulin-binding trimethoxyphenyl motif at C-2 of a thieno [2,3-d]pyrimidine fragment, enlarged by additional rings of different size and substit...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2020-03, Vol.189, p.112060-112060, Article 112060
Main Authors: Gold, Madeleine, Köhler, Leonhard, Lanzloth, Clarissa, Andronache, Ion, Anant, Shrikant, Dandawate, Prasad, Biersack, Bernhard, Schobert, Rainer
Format: Article
Language:English
Subjects:
Anti-angiogenesis
Anticancer drugs
Microtubule binding agents
Thienopyrimidine
Vascular-disruptive agents
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Summary:A series of forty-six 5,6-annulated 2-arylthieno [2,3-d]pyrimidin-4(3H)-ones were prepared as potentially pleiotropic anticancer drugs with variance in the tubulin-binding trimethoxyphenyl motif at C-2 of a thieno [2,3-d]pyrimidine fragment, enlarged by additional rings of different size and substitution. By assessing their cytotoxicity against various cancer cells, their influence on the polymerization of neat tubulin and the dynamics of microtubule and F-actin cytoskeletons, and their vascular-disrupting and anti-angiogenic activities in vitro and in vivo, structure-activity relations were identified which suggest the 3-iodo-4,5-dimethoxyphenyl substituted thienopyrimidine 2e as a promising anticancer drug candidate for further research. 2020 Elsevier Ltd. All rights reserved. Madeleine Gold, Leonhard Köhler, Clarissa Lanzloth, Ion Andronache, Shrikant Anant, Prasad Dandawate, Bernhard Biersack, Rainer Schobert. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2020.112060