Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

Bioorg Med Chem. 2014 Jan 1;22(1):204-10. doi: 10.1016/j.bmc.2013.11.035. Epub 2013 Nov 28.

Abstract

Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC₅₀: 1.41-1.76 μM) and 14e (IC₅₀: 1.72-2.01 μM) showed superior cytotoxic activity compared with etoposide (IC₅₀: 2.03 to >20 μM), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4'-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin's 4β position can significantly improve cytotoxic activity.

Keywords: Cytotoxic activity; Podophyllotoxin; Sulfonylurea; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents
  • Cell Line, Tumor
  • Humans
  • Podophyllotoxin / analogs & derivatives
  • Podophyllotoxin / chemical synthesis*
  • Podophyllotoxin / chemistry
  • Structure-Activity Relationship
  • Sulfonylurea Compounds / chemical synthesis*
  • Sulfonylurea Compounds / chemistry

Substances

  • Antineoplastic Agents
  • Sulfonylurea Compounds
  • Podophyllotoxin