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
-
- Angiogenesis Inhibitors/chemical synthesis
- Angiogenesis Inhibitors/metabolism
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Binding Sites
- CDC2 Protein Kinase/metabolism
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Chickens
- Drug Screening Assays, Antitumor
- G2 Phase Cell Cycle Checkpoints/drug effects
- Humans
- Molecular Docking Simulation
- Molecular Structure
- Protein Binding
- Protein Kinase Inhibitors/chemical synthesis
- Protein Kinase Inhibitors/metabolism
- Protein Kinase Inhibitors/pharmacology
- Pyrimidinones/chemical synthesis
- Pyrimidinones/metabolism
- Pyrimidinones/pharmacology*
- Structure-Activity Relationship
- Swine
- Thiophenes/chemical synthesis
- Thiophenes/metabolism
- Thiophenes/pharmacology*
- Tubulin/metabolism
- Tubulin Modulators/chemical synthesis
- Tubulin Modulators/metabolism
- Tubulin Modulators/pharmacology
- Zebrafish
- PubMed
- 31958738 Full text @ Eur. J. Med. Chem.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping