Synthesis of neolignans as microtubule stabilisers

Bioorg Med Chem. 2014 Feb 15;22(4):1342-54. doi: 10.1016/j.bmc.2013.12.067. Epub 2014 Jan 9.

Abstract

Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20 μM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.

Keywords: Acute oral toxicity; Anticancer; In silico studies; Lignans; Microtubules; Neolignans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Body Weight / drug effects
  • Cell Line, Tumor
  • Coumaric Acids / chemical synthesis*
  • Coumaric Acids / chemistry
  • Coumaric Acids / pharmacology
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Half-Life
  • Humans
  • Lignans / chemical synthesis*
  • Lignans / chemistry
  • Lignans / pharmacology
  • M Phase Cell Cycle Checkpoints / drug effects
  • MCF-7 Cells
  • Male
  • Mice
  • Molecular Docking Simulation
  • Protein Stability
  • Protein Structure, Tertiary
  • Tubulin / chemistry*
  • Tubulin / metabolism

Substances

  • Antineoplastic Agents
  • Coumaric Acids
  • Lignans
  • Tubulin
  • diethyl 4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate
  • diethyl 4-acetoxy-4'-hydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate