Background Resveratrol and its natural stilbene-containing derivatives have been extensively investigated as potential chemotherapeutic agents. The synthetic manipulation of the stilbene scaffold has led to the generation of new analogues with improved anticancer activity and better bioavailability. In the present study we investigated the anticancer activity of a novel trimethoxystilbene derivative (3,4,4'-trimethoxylstilbene), where two methoxyl groups are adjacent on the benzene ring (ortho configuration), and compared its activity to 3,5,4'-trimethoxylstilbene, whose methoxyl groups are in meta configuration. Results We provide evidence that the presence of the two methoxyl groups in ortho configuration renders 3,4,4'-trimethoxystilbene more efficient than the meta isomer in inhibiting cell proliferation and producing apoptotic death in colorectal cancer cells. Confocal microscopy of α- and γ-tubulin staining shows that the novel compound strongly depolymerizes the mitotic spindle and produces fragmentation of the pericentrosomal material. Computer assisted docking studies indicate that both molecules potentially interact with γ-tubulin, and that 3,4,4'-trimethoxystilbene is likely to establish stronger interactions with the protein. Conclusions These findings demonstrate the ortho configuration confers higher specificity for γ-tubulin with respect to α-tubulin on 3,4,4' trimethoxystilbene, allowing it to be defined as a new γ-tubulin inhibitor. A strong interaction with γ-tubulin might be a defining feature of molecules with high anticancer activity, as shown for the 3,4,4' isomer.

中文翻译：

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一种新型白藜芦醇衍生物通过抑制 γ-微管蛋白诱导有丝分裂停滞、中心体碎裂和癌细胞死亡。

背景白藜芦醇及其天然含芪衍生物已被广泛研究为潜在的化学治疗剂。芪支架的合成操作导致产生具有改进的抗癌活性和更好的生物利用度的新类似物。在本研究中，我们研究了一种新型三甲氧基芪衍生物（3,4,4'-三甲氧基芪）的抗癌活性，其中两个甲氧基在苯环上相邻（邻位构型），并将其活性与 3,5,4 '-三甲氧基芪，其甲氧基为间位构型。结果 我们提供的证据表明，邻位构型中两个甲氧基的存在使 3,4,4' -trimethoxystilbene 比间位异构体更有效地抑制结直肠癌细胞的细胞增殖和产生凋亡死亡。α-和γ-微管蛋白染色的共聚焦显微镜显示，新化合物强烈解聚有丝分裂纺锤体并产生中心体周围材料的碎片。计算机辅助对接研究表明，这两种分子都可能与 γ-微管蛋白相互作用，并且 3,4,4'-三甲氧基芪可能与蛋白质建立更强的相互作用。结论 这些发现表明，相对于 3,4,4' 三甲氧基芪的 α-微管蛋白，邻位构型赋予 γ-微管蛋白更高的特异性，使其被定义为一种新的 γ-微管蛋白抑制剂。与 γ-微管蛋白的强烈相互作用可能是具有高抗癌活性分子的决定性特征，