半合成螺旋霉素类似物的结构-抗肿瘤活性关系

Structure-antitumor activity relationship of semi-synthetic spicamycin analogues.

作者信息

Kamishohara M, Kawai H, Odagawa A, Isoe T, Mochizuki J, Uchida T, Hayakawa Y, Seto H, Tsuruo T, Otake N

机构信息

Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.

出版信息

J Antibiot (Tokyo). 1993 Sep;46(9):1439-46. doi: 10.7164/antibiotics.46.1439.

DOI:10.7164/antibiotics.46.1439

PMID:8226322

Abstract

Spicamycin, a nucleoside antibiotic containing fatty acids with a variety of chain lengths (C12-C18), showed potent antitumor activity against human gastric cancer SC-9 and human breast cancer MX-1 in a xenograft model. We have made several semi-synthetic spicamycin analogues (SPMs) which differed in the chain length of the fatty acid moiety, and examined their structure-antitumor activity relationship. The cytotoxic activities of SPMs depended on the chain length of the fatty acid moiety, with dodecanoyl, tetradecanoyl, hexadecanoyl and icosanoyl analogues (SPM VIII, SPM X, SPM XII and SPM XVI) exhibiting the most potent cytotoxic activity against P388 murine leukemia cells. SPM VIII showed the most activity against SC-9 in the human tumor xenograft model with the highest therapeutic index among SPMs. The antitumor activity of SPM VIII was superior to that of mitomycin C.

摘要

司派卡霉素是一种含有多种链长（C12 - C18）脂肪酸的核苷类抗生素，在异种移植模型中对人胃癌SC - 9和人乳腺癌MX - 1显示出强大的抗肿瘤活性。我们制备了几种脂肪酸部分链长不同的半合成司派卡霉素类似物（SPMs），并研究了它们的结构 - 抗肿瘤活性关系。SPMs的细胞毒性活性取决于脂肪酸部分的链长，其中十二烷酰、十四烷酰、十六烷酰和二十烷酰类似物（SPM VIII、SPM X、SPM XII和SPM XVI）对P388小鼠白血病细胞表现出最强的细胞毒性活性。在人肿瘤异种移植模型中，SPM VIII对SC - 9显示出最强活性，在SPMs中具有最高的治疗指数。SPM VIII的抗肿瘤活性优于丝裂霉素C。