恶性肿瘤发病率及死亡率逐年升高，以TopoII为靶点的化疗药物因双靶向引起的不良反应临床应用受限，开发选择性靶向TopoIIα拓扑异构酶抑制剂意义重大。Riccardin D(RD)是从苔类植物分离所得结构全新的大环双联卞类化合物，实验发现RD及其类似物对肺癌、结肠癌、肝细胞癌、白血病及口腔癌有较好疗效，但RD发挥抗肿瘤作用的靶点尚不明确。前期证实RD可选择性靶向TOPOIIα诱导癌细胞凋亡。在此基础上，采用同源模建、分子对接、SPR、细胞转染等技术深入探讨：1. RD与TOPOIIα靶酶的具体结合位点？2. RD是否通过调控HMGB1-RAGE-NF-κB信号通路对TOPOIIα产生抑制作用？阐明上述问题有利于以RD为代表的双联卞类化合物结构的进一步修饰优化，深入解析此类化合物抗肿瘤的分子机制对选择性靶向TOPOIIα的药物研发有着重要意义。

The incidence and mortality rate in malignant tumor increased recent years. The adverse effects caused by targeting both TopoIIα and TopoIIβ limited the clinical application of chemotherapy agents.It is significnat to develop inhibitors selectively targeting TopoIIα.Riccardin D(RD), a novel macrocyclic bisbibenzyl compounds extracted from the Chinese liverwort plant, and its analogues were found to be effective in vivo and vitro studies on inhibiting the growth of a variety of human tumors including non-small cell lung cancer, intestinal adenomaoral squamous carcinoma,hepatocellular carcinoma andleukemia. However,the accurate target of RD inhibiting tumor growth is not clear. Pre-test confirmed that RD induced apoptosis by selectively targeting TOPOIIα. Based on this, the homology modeling, molecular docking,SPR, transfected technology was used to explore two problems: 1. The specific binding sites of RD targeting TOPOIIα? 2.The regulation effect of HMGB1-RAGE-TLRs-NF-κB signaling pathway on the TOPOIIα inhibition produced by RD? To clarify the aboved issues will be helpful to modificate the structure of RD and its analogs.It is of great significance to develop the drug targeting TopoIIα after identifying the molecular mechanisms of such compounds.