Maeda H, Ichimura H, Satoh H, Ohtsuki K
J Antibiot (Tokyo). 1978 May;31(5):468-72. doi: 10.7164/antibiotics.31.468.
The toxicity of the bis-succinyl derivative of the protein antibiotic, neocarzinostatin, was compared with the parent compound, neocarzinostatin (NCS), in rats. The derivative was found to be about two to five fold more active than NCS in vivo. The antitumor activity in rats bearing eleven distinct Yoshida hepatoma ascitic cell lines was tested under four possible combinations with regard to sites of drug and tumor cell administration. The results indicate that the antitumor spectrum of the derivative had changed slightly. Antitumor activity in mice was also tested with L1210 and P388 lymphatic leukemia, and with B16 melanocarcinoma. When the effect of the derivative was compared with parental NCS at the molecular level with respect to the inhibition of DNA synthesis in vitro, the specific activities of the two were found to be almost identical. These results were interpreted to indicate that the succinyl derivative of NCS was more stable to inactivation and proteolytic break-down in vivo than NCS as observed previously in in vitro studies.
在大鼠中，对蛋白质抗生素新制癌菌素的双琥珀酰衍生物与母体化合物新制癌菌素（NCS）的毒性进行了比较。发现该衍生物在体内的活性比NCS高约两到五倍。在携带11种不同吉田肝癌腹水细胞系的大鼠中，针对药物和肿瘤细胞给药部位的四种可能组合测试了其抗肿瘤活性。结果表明，该衍生物的抗肿瘤谱略有变化。还用L1210和P388淋巴白血病以及B16黑色素瘤测试了小鼠的抗肿瘤活性。当在分子水平上比较该衍生物与亲本NCS对体外DNA合成的抑制作用时，发现两者的比活性几乎相同。这些结果被解释为表明，如先前在体外研究中观察到的那样，NCS的琥珀酰衍生物在体内比NCS对失活和蛋白水解分解更稳定。
