Design and multi-step synthesis of chalcone-polyamine conjugates as potent antiproliferative agents

Bioorg Med Chem Lett. 2017 Sep 15;27(18):4354-4357. doi: 10.1016/j.bmcl.2017.08.024. Epub 2017 Aug 13.

Abstract

The aim of this study is to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. 3-hydroxy-3',4,4',5'-tetramethoxychalcone (1) and 3',4,4',5'-tetramethoxychalcone (2) were selected as parent chalcones since they were found to be efficient anti-proliferative agents on various cancer cells. A series of ten chalcone-polyamine conjugates was obtained by reacting carboxychalcones with different polyamine tails. Chalcones 1 and 2 showed a strong cytotoxic activity against two prostatic cancer (PC-3 and DU-145) and two colorectal cancer (HT-29 and HCT-116) cell lines. Then, chalcone-spermine conjugates 7d and 8d were shown to be the most active of the series and could be considered as promising compounds for colon and prostatic cancer adjuvant therapy.

Keywords: Antiproliferative activity; Chalcones; Organic synthesis; Polyamines; Prostate and colorectal cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chalcone / chemistry
  • Chalcone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Polyamines / chemistry
  • Polyamines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Polyamines
  • Chalcone