Two novel C(7)-derivatives of natural anticancer agent colchicine were designed with the purpose to study their ability to induce tubulin clustering in cancer cells. The compounds were synthesized via amidation of N -deacetylcolchicine and Steglich esterification. The conjugate of colchicine with the guanosine derivative possesses moderate cytotoxicity to these cells (EC 50 = 13.7 µmol L −1 ) inducing the depolymerization of microtubules of human lung carcinoma A549 cells but does not stimulate the formation of tubulin clusters. The colchicine conjugate with the biphenyl moiety causes a strong tubulin clustering comparable to that of anticancer agent tubuloclustin. This effect was observed for the first time for the colchicine derivative bearing no substituent at the acetyl group capable of forming hydrogen bonds with target protein.

中文翻译：

---

C(7)-具有鸟苷和联苯部分的秋水仙碱衍生物：癌细胞中的分子建模、合成和微管蛋白聚集效应

设计了天然抗癌剂秋水仙碱的两种新型 C(7) 衍生物，目的是研究它们在癌细胞中诱导微管蛋白聚集的能力。这些化合物是通过 N-脱乙酰秋水仙碱的酰胺化和 Steglich 酯化合成的。秋水仙碱与鸟苷衍生物的结合物对这些细胞具有中等的细胞毒性（EC 50 = 13.7 µmol L -1 ），诱导人肺癌 A549 细胞微管解聚，但不刺激微管蛋白簇的形成。秋水仙碱与联苯部分的偶联物引起与抗癌剂微管凝集素相当的强微管蛋白簇。这种作用是首次观察到秋水仙碱衍生物在乙酰基上没有能够与目标蛋白形成氢键的取代基。