Design, synthesis and preliminary antiproliferative activity studies of new diheteroaryl thioether derivatives

Bioorg Med Chem Lett. 2017 Sep 15;27(18):4377-4382. doi: 10.1016/j.bmcl.2017.08.021. Epub 2017 Aug 18.

Abstract

A series of structurally new diheteroaryl thioether analogs was designed, prepared and screened toward MGC-803, MKN-45, EC-109 and H1650. Most of the target compounds displayed moderate to potent antiproliferative activities. Among them, compound 5 showed the best antiproliferative activity against the tested cell lines with the half maximal inhibitory concentration (IC50) values below 10μM. In addition, flow cytometry analysis showed that compound 5 increased Bax expression, down-regulated expression of Bcl-2, cleaved caspases-3/9, finally inducing apoptosis of MKN-45 cells as well asarrested the cell cycle at G2/M phase. This study suggests that the diheteroaryl thioethers are a class of emerging chemotypes for developing antitumor agents or biological probes, and compound 5 could serve as a good starting point to design new apoptosis inducers.

Keywords: Antiproliferative activity; Apoptosis; Cell cycle arrest; Diheteroaryl thioether.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antineoplastic Agents
  • Sulfides