title: Prolidase as a prodrug converting enzyme. III. Synthesis of proline analogues of melphalan and theirs susceptibility to the action of prolidase.
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.
authors.affiliation: Department of Medicinal Chemistry and Drug Technology, Medical Academy of Białystok.
authors.forename: A
authors.initials: A
authors.lastname: Bielawska
authors.forename: K
authors.initials: K
authors.lastname: Bielawski
authors.forename: J
authors.initials: J
authors.lastname: Pałka
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology*; D004150:Dipeptidases / Q000494:pharmacology*; D008558:Melphalan / Q000031:analogs & derivatives*; D011355:Prodrugs / Q000494:pharmacology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011355:Prodrugs; D004150:Dipeptidases; C022449:proline dipeptidase; D008558:Melphalan