STUDIES ON RA DERIVATIVES .5. SYNTHESIS AND ANTITUMOR-ACTIVITY OF ALA(2)-MODIFIED RA-VII DERIVATIVES

Authors
ITOKAWA H KONDO K HITOTSUYANAGI Y ISOMURA M TAKEYA K
Citation
H. Itokawa et al., STUDIES ON RA DERIVATIVES .5. SYNTHESIS AND ANTITUMOR-ACTIVITY OF ALA(2)-MODIFIED RA-VII DERIVATIVES, Chemical and Pharmaceutical Bulletin, 41(8), 1993, pp. 1402-1410
Citations number
12
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
Chemical and Pharmaceutical Bulletin → ACNP
ISSN journal
00092363
Volume
41
Issue
8
Year of publication
1993
Pages
1402 - 1410
Database
ISI
SICI code
0009-2363(1993)41:8<1402:SORD.S>2.0.ZU;2-U
Abstract
A number of RA-VII derivatives having various amino acids including pr oline (6), pipecolic acid (11), norvaline (12), ornithine (14), aspart ic acid (15) and methionine (20) in place of Ala2 have been synthesize d from RA-X methyl ester (3) and evaluated for cytotoxicity to P388 le ukemia and KB cells in vitro. Comparison of the cytotoxicity of these compounds suggests that the polarity and the length of the 2nd amino a cid residue affect the activity. An NMR study revealed that, in soluti on, 6 and 11 are locked in one conformational state, corresponding to conformer A of RA-VII.