PUBLICATION

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

Authors
Gold, M., Köhler, L., Lanzloth, C., Andronache, I., Anant, S., Dandawate, P., Biersack, B., Schobert, R.
ID
ZDB-PUB-200717-15
Date
2020
Source
European Journal of Medicinal Chemistry   189: 112060 (Journal)
Registered Authors
Keywords
Anti-angiogenesis, Anticancer drugs, Microtubule binding agents, Thienopyrimidine, Vascular-disruptive agents
MeSH Terms
  • Tubulin/metabolism
  • Molecular Structure
  • Binding Sites
  • Pyrimidinones/chemical synthesis
  • Pyrimidinones/metabolism
  • Pyrimidinones/pharmacology*
  • Swine
  • Protein Binding
  • Drug Screening Assays, Antitumor
  • Humans
  • Protein Kinase Inhibitors/chemical synthesis
  • Protein Kinase Inhibitors/metabolism
  • Protein Kinase Inhibitors/pharmacology
  • Molecular Docking Simulation
  • Animals
  • Structure-Activity Relationship
  • Cell Proliferation/drug effects
  • Chickens
  • G2 Phase Cell Cycle Checkpoints/drug effects
  • Thiophenes/chemical synthesis
  • Thiophenes/metabolism
  • Thiophenes/pharmacology*
  • CDC2 Protein Kinase/metabolism
  • Zebrafish
  • Angiogenesis Inhibitors/chemical synthesis
  • Angiogenesis Inhibitors/metabolism
  • Angiogenesis Inhibitors/pharmacology*
  • Cell Line, Tumor
  • Tubulin Modulators/chemical synthesis
  • Tubulin Modulators/metabolism
  • Tubulin Modulators/pharmacology
(all 31)
PubMed
31958738 Full text @ Eur. J. Med. Chem.
Abstract
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.
Genes / Markers
Figures
No images available
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Gold, M., Köhler, L., Lanzloth, C., Andronache, I., Anant, S., Dandawate, P., Biersack, B., Schobert, R. (2020) Synthesis and bioevaluation of new vascular-targeting and anti-angiogenic thieno[2,3-d]pyrimidin-4(3H)-ones. European Journal of Medicinal Chemistry. 189:112060.