Arylpyridines, arylpyrimidines and related compounds as potential modulator agents of the VEGF, hTERT and c-Myc oncogenes

  • Bioorg Med Chem. 2019 Mar 1;27(5):880-887. doi: 10.1016/j.bmc.2019.01.039.
Celia Martín-Beltrán  1 ,  María Sánchez-Peris  1 ,  Laura Conesa-Milián  1 ,  Eva Falomir  1 ,  Juan Murga  2 ,  Miguel Carda  1 ,  J Alberto Marco  3
Affiliations
  • 1. Dept. de Química Inorgánica y Orgánica, Universidad Jaume I, E-12071 Castellón, Spain.
  • 2. Dept. de Química Inorgánica y Orgánica, Universidad Jaume I, E-12071 Castellón, Spain. Electronic address: [email protected].
  • 3. Dept. de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia, Spain.
PMID: 30733086 DOI: 10.1016/j.bmc.2019.01.039
Abstract

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.

Keywords
Anticancer agents; Antiproliferative activity; Aza and diazabiphenyl derivatives; Gene targeting.