Komeshima N, Kawai H, Nakajima S, Watanabe M, Tsuruo T, Takeuchi T, Otake N
Pharmaceutical Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
J Antibiot (Tokyo). 1989 Sep;42(9):1424-9. doi: 10.7164/antibiotics.42.1424.
3'-Deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2), a morpholino anthracycline derived from 13-deoxo-10-hydroxycarminomycin (R20X2) was 16 times less cytotoxic than R20X2 against cultured P388 leukemia cells. The reduced cytotoxicity of MX2 was not explainable by intracellular or intranuclear concentration of the drug or by its DNA-intercalating activity. Binding of MX2 and R20X2 to DNA was measured, after isolating the DNA fraction from an incubation mixture of the drugs with P388 cells or with calf thymus DNA. The amount of R20X2 bound to the DNA was obviously larger than that of MX2, and was dependent on incubation time. These data suggest that the poor binding activity of MX2 to DNA contributes to its reduced cytotoxicity.
3'-脱氨基-3'-吗啉代-13-脱氧-10-羟基洋红霉素（MX2）是一种从13-脱氧-10-羟基洋红霉素（R20X2）衍生而来的吗啉代蒽环类药物，其对培养的P388白血病细胞的细胞毒性比R20X2低16倍。MX2细胞毒性降低无法用药物的细胞内或细胞核内浓度或其DNA嵌入活性来解释。在用药物与P388细胞或小牛胸腺DNA的孵育混合物中分离出DNA组分后，测量了MX2和R20X2与DNA的结合情况。与DNA结合的R20X2量明显大于MX2，且依赖于孵育时间。这些数据表明MX2与DNA的结合活性较差导致其细胞毒性降低。
