Miura S, Tanaka M, Yoshimura Y, Satoh H, Sakata S, Machida H, Matsuda A, Sasaki T
Department of Experimental Therapeutics, Kanazawa University, Japan.
Biol Pharm Bull. 1996 Oct;19(10):1311-5. doi: 10.1248/bpb.19.1311.
The in vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine (4'-thio-DMDC), was examined. 4'-Thio-DMDC inhibited the growth of various cell lines established from human solid cancers, particularly the growth of lung and bladder carcinomas and melanomas. 4'-Thio-DMDC exhibited potent antitumor activity against subcutaneously implanted murine sarcoma S-180 and human fibrosarcoma HT-1080 xenografts. It was shown that 4'-thio-DMDC suppressed cell growth by inhibiting cellular DNA synthesis, and phosphorylation of the 5'-position of its deoxyribose by deoxycytidine kinase was needed for its antitumor activity. 4'-Thio-DMDC is a poor substrate for cytidine deaminase, thus it is a promising agent for the treatment of malignant solid tumors because it will not be converted into its inactive uridine form.
对一种新型核苷4'-硫代-2'-脱氧-2'-亚甲基胞苷（4'-硫代-DMDC）的体外和体内抗肿瘤活性进行了研究。4'-硫代-DMDC抑制了源自人类实体癌的各种细胞系的生长，尤其是肺癌、膀胱癌和黑色素瘤细胞系的生长。4'-硫代-DMDC对皮下接种的小鼠肉瘤S-180和人纤维肉瘤HT-1080异种移植瘤表现出强大的抗肿瘤活性。结果表明，4'-硫代-DMDC通过抑制细胞DNA合成来抑制细胞生长，其抗肿瘤活性需要脱氧胞苷激酶对其脱氧核糖5'-位进行磷酸化。4'-硫代-DMDC是胞苷脱氨酶的不良底物，因此它是一种有前景的治疗恶性实体瘤的药物，因为它不会转化为无活性的尿苷形式。
