title: Synthesis of honokiol analogues and evaluation of their modulating action on VEGF protein secretion and telomerase-related gene expressions.
abstract: A group of 36 biphenyl derivatives structurally related to honokiol were synthesized by means of Suzuki coupling reactions. Their cytotoxicities were evaluated and compared to that of honokiol. Some of the compounds were then evaluated for their ability to downregulate the secretion of the VEGF protein and the expression of the VEGF, hTERT, and c-Myc genes; the two latter involved in the activation of telomerase in tumoral cells. Some of the synthetized derivatives showed promising pharmacological features as they exhibited IC50values in low micromolar range, good therapeutic margins, and a multiple mode of action on tumor cells based on the inhibition of VEGF and, at the same time, of the expression of genes related to the activation of telomerase.
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, Castellón, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-Peris
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, Castellón, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Murga
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, Castellón, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Falomir
authors.affiliation: Department of Inorganic and Organic Chemistry, University Jaume I, Castellón, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carda
authors.affiliation: Department of Organic Chemistry, University of Valencia, Burjassot, Spain.
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Marco
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D019098:Telomerase / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D017705:Lignans; D019098:Telomerase; D042461:Vascular Endothelial Growth Factor A; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: 
  
  hTERT
  
  ; 
  VEGF
  ; 
  c-Myc
  ; angiogenesis; gene regulation; honokiol analogues; telomerase