Prodrugs of 4'-demethyl-4-deoxypodophyllotoxin: synthesis and evaluation of the antitumor activity

Bioorg Med Chem Lett. 2002 Dec 2;12(23):3435-8. doi: 10.1016/s0960-894x(02)00758-8.

Abstract

A series of prodrugs of 4'-demethyl-4-deoxypodophyllotoxin (DDPT) including carbamates (3-8), a carbonate (9) and water-soluble amino acid derivatives (10-17) were prepared and tested for their antitumor activity. The carbamate 6 (2-hydroxyethylcarbamoyl-DDPT), carbonate 9 (2-chloroethyloxycarbonyl-DDPT), and most of amino acid prodrugs (12-17) showed enhanced antitumor activity.

MeSH terms

  • Amino Acids / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Carbamates / chemistry
  • Carbonates / chemistry
  • Drug Screening Assays, Antitumor
  • Drugs, Chinese Herbal
  • Humans
  • Hydrolysis
  • Lethal Dose 50
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / chemistry*
  • Podophyllotoxin / pharmacology*
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Amino Acids
  • Antineoplastic Agents
  • Carbamates
  • Carbonates
  • Drugs, Chinese Herbal
  • Prodrugs
  • deoxypodophyllotoxin
  • Podophyllotoxin