Synthesis and biological evaluation of S-acyl-3-thiopropyl prodrugs of N-phosphonoacetyl-L-aspartate (PALA).
The synthesis of new prodrugs of PALA characterised by the presence of S-acyl-3-thiopropyl, as enzyme-labile groups on the phosphonate moiety of PALA, is reported. The cytotoxic activities of PALA prodrugs were determined against human cell line (SW1573 lung carcinoma cells). A number of prodrugs bearing S-pivaloyl as acyl groups displayed cytotoxic activity in the same order of magnitude of PALA.
Laboratoire de chimie biomoléculaire, UMR 5032, Université Montpellier II, ENSCM, 8 rue de l'Ecole normale, 34296 Montpellier cedex 5, France.
Valérie
V
Gagnard
Alain
A
Leydet
Véronique
V
Le Mellay
Marielle
M
Aubenque
Alain
A
Morère
Jean-Louis
JL
Montero
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds
D000970:Antineoplastic Agents; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid