Prolidase as a prodrug converting enzyme. III. Synthesis of proline analogues of melphalan and theirs susceptibility to the action of prolidase

Rocz Akad Med Bialymst. 1999:44:190-9.

Abstract

The feasibility to targeting prolidase as an antineoplastic prodrug-converting enzyme has been examined. The synthesis of proline analogues of melphalan (well known antineoplastic agent) conjugated through imido-bond (potential target for prolidase action) has been performed. One of the compounds, N-[[[[(S)-carboxy]pyrrolidin-1-yl]carbonyl]methyl]-4-[bis(2-chloro ethyl) amino]-2-phenylalanine, was found as very good prolidase substrate with susceptibility over 2 fold higher compared to standard, endogenous its substrate--Gly-L-Pro. It suggests that targeting of prolidase as a proline analogue of melphalan-converting enzyme may serve as a novel strategy in therapy of neoplastic diseases.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / chemical synthesis*
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Dipeptidases / pharmacology*
  • Melphalan / analogs & derivatives*
  • Prodrugs / pharmacology*

Substances

  • Antineoplastic Agents, Alkylating
  • Prodrugs
  • Dipeptidases
  • proline dipeptidase
  • Melphalan