Synthesis and antitumor activities of glycine-exchanged analogs of spicamycin.
A series of SPM VIII analogs were synthesized to investigate the effect of the amino acid moiety on the antitumor activity. The L-threonine analog and the glycylglycine analog of SPM VIII showed much higher cytotoxicity to P388 murine leukemia cells (IC50 5.8 nM and 0.11 nM, respectively) than SPM VIII (IC50 25nM). However, replacement of the glycine moiety with other amino acids greatly reduced the antitumor activity against COL-1 human colon cancer xenograft model. This study indicated that the glycine moiety of SPM VIII is crucial for the antitumor effect.
Sakai
T
T
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Kawai
H
H
Kamishohara
M
M
Odagawa
A
A
Suzuki
A
A
Uchida
T
T
Kawasaki
T
T
Tsuruo
T
T
Otake
N
N
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011684:Purine Nucleosides / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000903:Antibiotics, Antineoplastic; D011684:Purine Nucleosides; C015502:septacidin