Lead Optimization of 2-Cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides for Targeting the HER-2 Overexpressed Breast Cancer Cell Line SKBr-3

Molecules. 2015 Oct 7;20(10):18246-63. doi: 10.3390/molecules201018246.

Abstract

Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 1-18 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC50 = 17.44 ± 0.01 µM to 53.29 ± 0.33 µM. (2Z)-2-(3-Hydroxybenzylidene)-N-(3-methoxyphenyl)hydrazinecarbothioamide (12, IC50 = 17.44 ± 0.01 µM) was found to be most potent compound of this series targeting HER-2 overexpressed breast cancer cells compared to the standard drug 5-fluorouracil (5-FU) (IC50 = 38.58 ± 0.04 µM). Compound 12 inhibited the cellular proliferation via DNA degradation.

Keywords: BT-474 cells; HER-2; SKBr-3 cells; cancer stem cells; thiosemicarbazones.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA, Neoplasm / drug effects
  • Female
  • Fluorouracil / pharmacology
  • Guanidines / chemical synthesis*
  • Guanidines / chemistry
  • Guanidines / pharmacology*
  • Humans
  • Lead / chemistry*
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics

Substances

  • DNA, Neoplasm
  • Guanidines
  • Protein Kinase Inhibitors
  • Lead
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Fluorouracil