Hong C I, Kirisits A J, Buchheit D J, Nechaev A, West C R
Cancer Drug Deliv. 1986 Spring;3(2):101-13. doi: 10.1089/cdd.1986.3.101.
Three 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates of 1-S-alkyl-phospholipids (thioether phospholipids) were tested for their antitumor efficacies against L1210 and P388 leukemia in mice. These include 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-rac-1-S-hexadecyl-2-0-palmitoyl-1-thioglycerol (ara-CDP-beta-palmitoyl-DL-thiochimyl alcohol, I), ara-CDP-rac-1-S-octadecyl-2-0-palmitoyl-1-thioglycerol (ara-CDP-beta-palmitoyl-DL-thiobatyl alcohol, II), and ara-CDP-rac-1-S-octadecyl-2-0-hexadecyl-1-thioglycerol (ara-CDP-beta-cetyl-DL-thiobatyl alcohol, III). Conjugates I and II produced significant increase in life span (293-379%) and longterm survivors among mice bearing i.p. implanted L1210 lymphoid leukemia at a total dose of 400 mg (389-400 mumol)/kg. Conjugate II also displayed a strong antitumor activity against i.c. implanted L1210 leukemia in mice with an ILS range of 160-200% at a total dose of 300-450 mg (292-438 mumol/kg. Significant schedule dependency was not observed when the conjugates were administered i.p. once daily with following schedules: qd l; 1,5, 9; 1-5; and 1-9, but single doses typically produced the best effects. The i.p. administration of conjugate II gave the best results on survival of i.p. inoculated L1210 leukemic mice, then followed by the s.c. and i.m. treatments. The i.v. treatment produced a lower activity than the others. Conjugate II also exhibited a strong antitumor activity against i.p. implanted P388 leukemia in mice with ILS values of greater than 255-greater than 329% with 3-5 45-day survivors at a total dose of 300-500 mg (292-486 mumol)/kg (qd 1 or 1-5). The new conjugates I and II displayed a comparable or somewhat higher activity than the previous diacyl and 1-0-alkyl analogs.
测试了三种1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，ara-C）与1-S-烷基磷脂（硫醚磷脂）的缀合物对小鼠L1210和P388白血病的抗肿瘤疗效。这些缀合物包括1-β-D-阿拉伯呋喃糖基胞嘧啶5'-二磷酸-rac-1-S-十六烷基-2-O-棕榈酰-1-硫代甘油（阿糖胞苷二磷酸-β-棕榈酰-DL-硫代鞘氨醇，I）、阿糖胞苷二磷酸-rac-1-S-十八烷基-2-O-棕榈酰-1-硫代甘油（阿糖胞苷二磷酸-β-棕榈酰-DL-硫代巴豆醇，II）和阿糖胞苷二磷酸-rac-1-S-十八烷基-2-O-十六烷基-1-硫代甘油（阿糖胞苷二磷酸-β-十六烷基-DL-硫代巴豆醇，III）。缀合物I和II使接种L1210淋巴白血病的小鼠的寿命显著延长（293%-379%），并出现长期存活者，总剂量为400 mg（389-400 μmol）/kg，腹腔注射。缀合物II对小鼠脑内接种的L1210白血病也显示出强大的抗肿瘤活性，总剂量为300-450 mg（292-438 μmol/kg）时，生命延长率（ILS）为160%-200%。当缀合物按以下给药方案每天腹腔注射一次时，未观察到明显的给药时间依赖性：每日一次；第1、5、9天；第1-5天；以及第1-9天，但单剂量给药通常效果最佳。缀合物II腹腔注射给药对腹腔接种L1210白血病小鼠的生存效果最佳，其次是皮下和肌肉注射给药。静脉注射给药的活性低于其他给药方式。缀合物II对小鼠腹腔接种的P388白血病也表现出强大的抗肿瘤活性，总剂量为300-500 mg（292-486 μmol）/kg（每日一次或第1-5天给药）时，ILS值大于255%-大于329%，有3-5只小鼠存活45天。新的缀合物I和II显示出与先前的二酰基和1-O-烷基类似物相当或略高的活性。
