Synthesis and Anticancer Activity Comparison of Phenylalkyl Isoselenocyanates With Corresponding Naturally Occurring and Synthetic Isothiocyanates

J Med Chem. 2008 Dec 25;51(24):7820-6. doi: 10.1021/jm800993r.

Abstract

Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure-activity relationship comparison of ISCs with ITCs and effect of the increasing alkyl chain length in inhibiting cancer cell growth were evaluated on melanoma, prostate, breast, glioblastoma, sarcoma, and colon cancer cell lines. IC(50) values for ISC compounds were generally lower than their corresponding ITC analogues. Similarly, in UACC 903 human melanoma cells, the inhibition of cell proliferation and induction of apoptosis were more pronounced with ISCs compared to ITCs. Further, ISCs and ITCs effectively inhibited melanoma tumor growth in mice following intraperitoneal xenograft. A similar reduction in tumor size was observed at 3 times lower doses of ISCs compared to corresponding ITCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Drug Screening Assays, Antitumor*
  • Humans
  • Inhibitory Concentration 50
  • Isothiocyanates / chemistry*
  • Mice
  • Models, Chemical
  • Neoplasm Transplantation
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Isothiocyanates