Improved anticancer and antiparasitic activity of new lawsone Mannich bases

Eur J Med Chem. 2017 Jan 27:126:421-431. doi: 10.1016/j.ejmech.2016.11.043. Epub 2016 Nov 22.

Abstract

Substituted lawsone Mannich bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. The new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human cancer cell lines associated with ROS formation. In addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic Trypanosoma brucei brucei cells via deformation of the microtubule cytoskeleton. The N-hexadecyl compound 2c was also highly active against locally isolated Entamoeba histolytica parasite samples exceeding the activity of metronidazole.

Keywords: Anticancer drugs; Antiparasitic drugs; Lawsone; Mannich base.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Drug Design
  • Entamoeba histolytica / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Mannich Bases / chemistry*
  • Naphthoquinones / chemistry*
  • Naphthoquinones / pharmacology*
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei brucei / drug effects

Substances

  • Antineoplastic Agents
  • Mannich Bases
  • Naphthoquinones
  • Trypanocidal Agents
  • lawsone