6533b839fe1ef96bd12a5aab
RESEARCH PRODUCT
Arylpyridines, arylpyrimidines and related compounds as potential modulator agents of the VEGF, hTERT and c-Myc oncogenes.
Miguel CardaEva FalomirLaura Conesa-miliánJ. Alberto MarcoMaría Sánchez-perisCelia Martín-beltránJuan Murgasubject
Honokiolantiproliferative activityVascular Endothelial Growth Factor APyridinesClinical Biochemistryaza and diazabiphenyl derivativesPharmaceutical ScienceDown-RegulationGene ExpressionAntineoplastic Agents01 natural sciencesBiochemistrygene targetingProto-Oncogene Proteins c-mycchemistry.chemical_compoundanticancer agentsCell Line TumorDrug DiscoveryGene expressionHumansSecretionTelomerase reverse transcriptaseMolecular BiologyTelomeraseCell ProliferationNatural product010405 organic chemistryOrganic ChemistryGene targeting0104 chemical sciences010404 medicinal & biomolecular chemistryVascular endothelial growth factor AHEK293 CellsPyrimidineschemistryCell cultureProtein BiosynthesisCancer researchMolecular Medicinedescription
Twenty-four derivatives structurally related to honokiol have been synthesized and biologically evaluated. IC50 values were determined towards the HT-29, MCF-7 and HEK-293 cell lines. Some of these derivatives exhibited comparable or lower IC50 values than honokiol towards the HT-29 and MCF-7 cell lines or else higher selectivity indexes than the natural product. Twelve selected derivatives were evaluated for their ability to inhibit the expression of the VEGFA, hTERT and c-Myc genes and also to inhibit the production of total c-Myc protein and the secretion of the VEGF protein. One of the most promising compounds, 3-(2,4-dimethoxyphenyl)pyridine, may be a good candidate for further studies as an anticancer agent as it is able to improve the effect shown by honokiol in downregulating all gene expression and protein production at a safe concentration for non-tumor cells.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-03-01 | Bioorganicmedicinal chemistry |