Synthesis of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-β-carboline analogs as potential antitumor agents

Mar Drugs. 2011 Feb 10;9(2):256-277. doi: 10.3390/md9020256.

Abstract

A series of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-β-carboline analogs have been synthesized and evaluated for antitumor activity against human tumor cells including KB, DLD, NCI-H661, Hepa, and HepG2/A2 cell lines. Among these, compounds 2, 6, 7, and 9 exhibited the most potent and selective activity against the tested tumor cells. As for inhibition of topoisomerase II, compounds 1-14 and 18 showed better activity than etoposide. Among them, compounds 3, 4, 7, 9, and 10 exhibited potent activity. The structure and activity relationship (SAR) study revealed correlation between carbon numbers of the side chain and biological activities. The molecular complex with DNA for compound 2 was proposed.

Keywords: antitumor agents; carbazolyl-1,2,3,4-tetrahydro-β-carbolines; carbazolyl-3,4-dihydro-β-carbolines; structure activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Carbazoles / chemistry*
  • Carbolines / chemical synthesis*
  • Carbolines / pharmacology*
  • Cell Line, Tumor
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • KB Cells
  • Models, Molecular
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Carbazoles
  • Carbolines