Synthesis and pharmacological evaluation of novel bisindolylalkanes analogues

Bioorg Med Chem. 2013 Dec 15;21(24):7624-7. doi: 10.1016/j.bmc.2013.10.034. Epub 2013 Nov 6.

Abstract

In an effort to develop potent anti-cancer chemopreventive agents that act on topoisomerase II, a novel series of bisindolylalkanes analogues such as 3,3'-(thiochroman-4,4-diyl)bis(1H-indole) are synthesized. Structures of all compounds are elucidated by (1)H NMR, (13)C NMR and HRMS. Anti-proliferative activities for all of these compounds are investigated by the method of MTT assay on 7 human cancer lines. Most of them showed antitumor activities in vitro, the half maximal inhibitory concentration (IC50) value is 7.798 μg/mL of 3a against MCF7. Compound 3a showed comparable topoisomerase II inhibitory activity to etoposide (VP-16) at 100 μM concentration. The rest of the compounds also showed varying degree topoisomerase II inhibitory activity.

Keywords: Anticancer; Bisindolylalkane; Indole; Thiochroman-4-one; Topoisomerase II.

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
  • DNA Topoisomerases, Type II / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Molecular Structure
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemical synthesis
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / pharmacology*

Substances

  • Antineoplastic Agents
  • Indoles
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II