烯二炔类大分子抗肿瘤抗生素C1027抗菌与抗肿瘤活性差异的研究

Studies of antibiotic and antitumor activity by enediyne antitumor antitiotic C 1027

Ｃ１０２７具有极强杀伤肿瘤细胞活性，作用靶点在ＤＮＡ，但Ｃ１０２７ 的抗菌活性不强，如能了解差别出现的原因，就可进一步掌握Ｃ１０２７的抗菌作用机制，并为将来在临床上确定其应用范围打下良好基础。对Ｃ１０２７ 的抗肿瘤活性与抗菌活性的差异的初步研究结论如下：大分子Ｃ１０２７ 与小分子博莱霉素Ａ５ 相比，对肿瘤细胞抑制作用明显高于后者；对细菌的抑制作用却明显低于博莱霉素Ａ５；对支原体的抑制作用略大于博莱霉素Ａ５ 。Ｃ１０２７（１００～０．０１ｍ ｇ／Ｌ）对大肠埃希氏菌Ｂ原生质体ＤＮＡ合成几乎无抑制作用，同对大肠埃希氏菌Ｂ菌体的ＤＮＡ合成抑制作用相比，差别不大。细胞壁并非阻碍Ｃ１０２７损伤大肠埃希氏菌ＢＤＮＡ的主要因素。

The antibiotic C1027 showed extremely potent cytotoxicity toward cultured cancer cells and markedly inhibited the growth of transplantable tumors in mice, but it had weak activity toward the bacteria. Knowing the reason of the diversity will be very useful to clarify the mechanism of C1027 deeply and it will be helpful to determine the clinical application of C1027. In this study, we investigated the antibacterial, antitumor and antimycoplasma activities of C1027 and bleomycin A 5; the effect on the synthesis of DNA in E.coli B and its plasma cell; the anti E.coli B and anti competent E.coli B activities of C1027 and penicillin. Compared with bleomycin A 5, C1027 showed greater cytotoxicities to tumor cells, lower activities to bacterial. and it showed a slighthly more potent activities toward mycoplasma. C1027 (100~0.01mg/L) had no effect on the synthesis of DNA of E.coli B plasma cells as well as the synthesis of DNA of E.coli B cells. The cell wall was not the main reason of the between the cytotoxicities of C1027 to tumor cells and to bacterial.