Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines.

In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared. First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets. The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design.

为了更好地理解中药天然化合物的结构特征，对MACCS - II药物数据报告（MDDR）中的类药化合物、可用化学目录（ACD）中的非类药化合物以及中药化合物数据库（TCMCD）中的天然化合物的骨架结构进行了探索和比较。 首先，通过使用三种骨架表示方法，包括Murcko框架、骨架树以及具有不同复杂性和侧链的环系，从ACD、MDDR和TCMCD中提取不同的骨架。然后，通过检查每个数据集中骨架的累积频率，我们观察到骨架树的一级骨架在表示化合物库的骨架多样性方面比其他骨架结构更具优势。通过比较MDDR、ACD和TCMCD中呈现的骨架结构的相似性，不仅在MDDR和TCMCD之间，而且在MDDR和ACD之间都观察到了结构重叠。最后，使用树状图对骨架树的一级骨架进行聚类，并可视化三个数据集的骨架空间。 对MDDR、ACD和TCMCD的骨架结构分析表明，平均而言，MDDR中的类药分子具有最高的多样性，而TCMCD中的天然化合物具有最高的复杂性。根据树状图，可以观察到MDDR中存在的一级骨架比TCMCD和ACD中的具有更高的多样性。然而，MDDR中一些高频的代表性骨架与TCMCD和ACD中的骨架在结构上具有相似性，这表明TCMCD和ACD中的一些骨架可能是基于片段和从头药物设计的潜在类药片段。