Cinnamic acid derived oxazolinium ions as novel cytotoxic agents

Eur J Med Chem. 2002 Jul;37(7):607-16. doi: 10.1016/s0223-5234(02)01375-2.

Abstract

Substituted cinnamoyl chlorides, 11, were converted into (2-hydroxyethyl)-oxazolinium chlorides 14, N,N-bis-(2-chloroethyl)amides 16 and (2-chloroethyl)-oxazolinium chlorides 17. Although derivatives 14 which possess electron-donating substituents (Me or MeO) were more potent than those substituted by electron-withdrawing groups (NO(2), Cl or CF(3)), the difference in cytotoxic actin was not significant. Modification of the lipophilic character in a series of alkoxy-substituted derivatives 14 led to more active compounds, where 14t that possesses a 4-octyloxy-phenyl-substituent was the most potent and displayed cytotoxic activity in the microM range. It is assumed that the oxazolinium salts act as alkylating agents, and undergo nucleophilic attack on the methylene adjacent to the ring oxygen where the oxazolinium ring parallels the aziridinium ring intermediate found in classical alkylating agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Cinnamates / chemistry
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cinnamates
  • Oxazoles
  • cinnamic acid