title: Antineoplastic activity of didemnin congeners: nordidemnin and modified chain analogues.
abstract: Nordidemnin (2), a natural analogue of the marine cyclodepsipeptide didemnin B (1b), showed cytotoxic activity against L1210 leukemia and antineoplastic activity against P388 leukemia as well as B16 melanoma; nordidemnin (2) was as active as didemnin B (1b). The influence of synthetic modifications in the linear peptidic chain on in vitro and in vivo activity was also studied. Replacement of the terminal lactyl residue by mandelyl and 3-(p-hydroxyphenyl)propionyl residues in compounds 3 and 4, respectively, did not affect the cytotoxic activity against L1210 leukemia (ID50 of 1.1 nM and 1.2 nM, respectively) or the in vivo activity against P388 leukemia. Unlike these aromatic substituants, the lipophilic palmityl residue induced a dramatic loss in cytotoxic activity. The inverted chirality of the MeLeu joining residue in compound 6 caused a marked reduction in the in vitro activity.
authors.affiliation: CCIPE, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Jouin
authors.forename: J
authors.initials: J
authors.lastname: Poncet
authors.forename: M N
authors.initials: MN
authors.lastname: Dufour
authors.forename: A
authors.initials: A
authors.lastname: Aumelas
authors.forename: A
authors.initials: A
authors.lastname: Pantaloni
authors.forename: S
authors.initials: S
authors.lastname: Cros
authors.forename: G
authors.initials: G
authors.lastname: François
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002621:Chemistry; D047630:Depsipeptides; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D010456:Peptides, Cyclic; C067388:nordidemnin B; C030051:didemnins