Kaneda S, Hour-Young C, Yazawa K, Takahashi K, Mikami Y, Arai T
Jpn J Cancer Res. 1986 Oct;77(10):1043-9.
Saframycins Yd-1 and Y3, which have an amino functional group in the side chain, were recently obtained by a directed biosynthesis. Twenty-eight side chain-modified chemical derivatives were prepared from these saframycins, and their in vitro and in vivo antitumor activities were studied. Among these new derivatives, three saframycins, namely, two N-acyl derivatives, pivaloyl- and n-caproylsaframycin Y3, and one water-soluble type, saframycin Yd-1.HCl, were found to show marked antitumor activity against L1210 mouse leukemia cells. Further studies of these saframycin derivatives using B16-F10 melanoma and Lewis lung carcinoma indicated that all three saframycins are also active against B16-F10 melanoma; saframycin Yd-1.HCl showed the greatest prolongation of survival time. Marked inhibition of spontaneous metastasis of Lewis lung carcinoma was observed in mice treated with these new derivatives. Structure-activity relationships among these semisynthetic saframycins are discussed.
最近通过定向生物合成获得了在侧链中具有氨基官能团的沙弗霉素Yd-1和Y3。从这些沙弗霉素制备了28种侧链修饰的化学衍生物，并研究了它们的体外和体内抗肿瘤活性。在这些新衍生物中，发现三种沙弗霉素，即两种N-酰基衍生物，新戊酰基和正己酰基沙弗霉素Y3，以及一种水溶性类型的沙弗霉素Yd-1.HCl，对L1210小鼠白血病细胞显示出显著的抗肿瘤活性。使用B16-F10黑色素瘤和Lewis肺癌对这些沙弗霉素衍生物进行的进一步研究表明，所有三种沙弗霉素对B16-F10黑色素瘤也有活性；沙弗霉素Yd-1.HCl显示出最长的存活时间延长。在用这些新衍生物治疗的小鼠中观察到Lewis肺癌自发转移受到明显抑制。讨论了这些半合成沙弗霉素之间的构效关系。
