Neuroblastoma is an aggressive and drug-resistant refractory cancer. The human high-risk neuroblastoma cell line, SK-N-AS (non-amplified N-myc) is derived from stromal cells and it is resistant to treatment with retinoic acid (1, RA), which is a chemotherapeutic agent used to induce neuronal cellular differentiation of neuroblastomas. We have developed p-dodecylaminophenol (3, p-DDAP), based on N-(4-hydroxyphenyl)retinamide (2, 4-HPR), a synthetic amide of 1, since 1 and 2 are associated with the side-effect of nyctalopia. In order to evaluate the effects of 3 on high-risk neuroblastomas, we employed SK-N-AS cells as well as a second high-risk human neuroblastoma cell line, IMR-32, which is derived from neuronal cells (amplified N-myc, drug sensitive). Compound 3 suppressed cell growth of SK-N-AS and IMR-32 cells more effectively than 1, 2, p-decylaminophenol (4, p-DAP), N-(4-hydroxyphenyl)dodecananamide (5, 4-HPDD) or N-(4-hydroxyphenyl)decananamide (6, 4-HPD). In SK-N-AS cells, 3 induced G₀/G₁ arrest and apoptosis to a greater extent than 1 and 2. In IMR-32 cells, 3 induced apoptosis to a similar extent as 1 and 2, potentially by inhibiting N-myc expression. In addition, i.p. administration of 3 suppressed tumor growth in SK-N-AS-implanted mice in vivo. Since 3 showed no effects on blood retinol concentrations, in contrast to reductions following the administration of 2, it exhibited excellent anticancer efficacy against high-risk neuroblastoma SK-N-AS and IMR-32 expressing distinct levels of N-myc. Compound 3 may have potential for clinical use in the treatment of refractory neuroblastoma with reduced side effects.

神经母细胞瘤是一种侵袭性且耐药的难治性癌症。人类高危神经母细胞瘤细胞系SK-N-AS（非扩增N-myc）衍生自基质细胞，对视黄酸（1，RA）具有抗药性，视黄酸是一种化学诱导剂，可诱导神经母细胞瘤的神经元细胞分化。我们已经开发p -dodecylaminophenol（3，对- DDAP），基于ñ - （4-羟基苯基）视黄酰胺（2，4-HPR），的合成酰胺1中，由于1和2与的副作用相关联的夜视。为了评价3的效果在高危神经母细胞瘤上，我们采用了SK-N-AS细胞以及第二种高危人神经母细胞瘤细胞系IMR-32，该细胞系来源于神经元细胞（扩增的N-myc，对药物敏感）。化合物3 SK-N-AS和IMR-32细胞的抑制细胞生长更有效地比1，2，p -decylaminophenol（4，对- DAP），ñ - （4-羟基苯基）dodecananamide（5，4-HPDD）或ñ - （4-羟基苯基）decananamide（6，4-HPD）。在SK-N-AS细胞中，3诱导G ₀ / G ₁阻滞和凋亡的程度大于1和2。在IMR-32细胞中，3可能通过抑制N-myc表达而诱导细胞凋亡，其程度与1和2相似。另外，腹膜内给予3抑制了SK-N-AS植入小鼠体内肿瘤的生长。由于3对血液中的视黄醇浓度没有影响，与2给药后的减少相比，它对表现出不同水平的N-myc的高危神经母细胞瘤SK-N-AS和IMR-32表现出优异的抗癌功效。化合物3具有潜在的临床用途，可用于治疗难治性神经母细胞瘤，且副作用减少。