Sakai T, Kawai H, Kamishohara M, Odagawa A, Suzuki A, Uchida T, Kawasaki T, Tsuruo T, Otake N
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
J Antibiot (Tokyo). 1995 Jun;48(6):504-8. doi: 10.7164/antibiotics.48.504.
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.
合成了一系列SPM VIII类似物，以研究氨基酸部分对抗肿瘤活性的影响。SPM VIII的L-苏氨酸类似物和甘氨酰甘氨酸类似物对P388小鼠白血病细胞的细胞毒性（IC50分别为5.8 nM和0.11 nM）比SPM VIII（IC50为25 nM）高得多。然而，用其他氨基酸取代甘氨酸部分大大降低了对COL-1人结肠癌异种移植模型的抗肿瘤活性。这项研究表明，SPM VIII的甘氨酸部分对抗肿瘤作用至关重要。
