Studies on RA derivatives. V. Synthesis and antitumor activity of Ala2-modified RA-VII derivatives.
A number of RA-VII derivatives having various amino acids including proline (6), pipecolic acid (11), norvaline (12), ornithine (14), aspartic acid (15) and methionine (20) in place of Ala2 have been synthesized from RA-X methyl ester (3) and evaluated for cytotoxicity to P388 leukemia and KB cells in vitro. Comparison of the cytotoxicity of these compounds suggests that the polarity and the length of the 2nd amino acid residue affect the activity. An NMR study revealed that, in solution, 6 and 11 are locked in one conformational state, corresponding to conformer A of RA-VII.
Itokawa
H
H
Tokyo College of Pharmacy, Japan.
Kondo
K
K
Hitotsuyanagi
Y
Y
Isomura
M
M
Takeya
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C043548:RA VII