Synthesis and biological evaluation of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one and its aminomethyl derivatives

J Enzyme Inhib Med Chem. 2015 Jun;30(3):383-8. doi: 10.3109/14756366.2014.940934. Epub 2014 Jul 28.

Abstract

Aminomethyl derivatives of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one, designed as new cytotoxins, were synthesized and evaluated in terms of their cytotoxic activities. The compounds have low CC50 values in the low micromolar range against HL-60 neoplasms and HSC-2, HSC-3 and HSC-4 carcinoma cells. In general, the average CC50 values of these compounds were higher towards HGF, HPC and HPLF non-malignant cells, which reveals the tumour-selectivity of these aminomethyl derivatives, Mannich bases. Using specific concentrations of compounds 4 and 6 caused cleavage of PARP1 in HSC-2 cells but not HGF cells, which may be a contributing factor to cytotoxicities and the tumour-selectivities.

Keywords: Aminomethyl derivatives; CC50; PARP1; cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / analogs & derivatives*
  • Curcumin / chemical synthesis
  • Curcumin / chemistry
  • Curcumin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amines
  • Antineoplastic Agents
  • Curcumin