Spiropyrans have been investigated for their thermo- and photochromic characteristics, but their biotherapeutic properties have not been addressed. We report anti-proliferative properties of a novel dinaphthospiropyran analogue (1). The compound 1 was synthesized by a simple and expedient method using a one-pot acid-catalyzed aldol condensation of 2-hydroxy-1-naphthaldehyde with 4-piperidone followed by an acetalization reaction. Compound 1 was submitted to anticancer drug screen in the National Cancer Institute’s panel of 60 human tumor cell lines. The average concentration of 1 to inhibit 50% cell growth was 5.4 ± 0.23 µM. All cell lines responded at almost the same concentration, suggesting that the action of 1 is not selective for cancer of origin. COMPARE analysis of dose-response data revealed interaction with tubulin as the possible mechanism of action of 1. At molecular level, 1 induced tubulin reorganization in colon cancer HCT-116 cells. Under cell-free conditions, the efficacy of 1 to inhibit tubulin polymerization was comparable to that of paclitaxel and vinblastine. Molecular docking showed that compound 1 binds to the colchicine-binding site of tubulin. We conclude that dinaphthospiropyrans present a novel scaffold for the development of tubulin inhibitors.

已经研究了螺吡喃的热致变色和光致变色特性，但尚未解决它们的生物治疗特性。我们报告了一种新型二萘螺吡喃类似物的抗增殖特性 ( 1)。使用一锅酸催化的 2-羟基-1-萘醛与 4-哌啶酮的醛醇缩合，然后进行缩醛化反应，通过简单而方便的方法合成了化合物1。化合物1被提交到美国国家癌症研究所的 60 个人类肿瘤细胞系面板中进行抗癌药物筛选。1抑制 50% 细胞生长的平均浓度为 5.4 ± 0.23 µM。所有细胞系的反应浓度几乎相同，表明1对原发癌没有选择性。剂量反应数据的比较分析揭示了与微管蛋白的相互作用是1的可能作用机制。在分子水平上，1诱导结肠癌 HCT-116 细胞中的微管蛋白重组。在无细胞条件下，1抑制微管蛋白聚合的功效与紫杉醇和长春碱的功效相当。分子对接表明，化合物1与微管蛋白的秋水仙碱结合位点结合。我们得出结论，dinaphthospiropyrans 为微管蛋白抑制剂的开发提供了一种新的支架。