ABSTRACT

Cancer remains one of the leading causes of death in humans, and new drug substances are therefore being developed. Thus, the anti-cancer activity of xanthene derivatives has become an important topic in the development of new and potent anti-cancer drug substances. Previously published novel series of xanthen-3-one and xanthen-1,8-dione derivatives have been synthesized in one of our laboratories and showed anti-proliferative activity in HeLa cancer cell lines. This series serves as a good basis to develop quantitative structure–activity relationship (QSAR), to study the relations between anti-proliferative activity and chemical structures. A QSAR model has been derived that relies only on two-dimensional molecular descriptors, providing mechanistic insight into the anti-proliferative activity of xanthene derivatives. The model is validated internally and externally and additionally with the set of inactive compounds of the original data, confirming model applicability for the design and discovery of novel xanthene derivatives. The QSAR model is available at the QsarDB repository (http://dx.doi.10.15152/QDB.237).

摘要

癌症仍然是人类死亡的主要原因之一，因此正在开发新的药物。因此，x吨衍生物的抗癌活性已经成为开发新型有效的抗癌药物中的重要课题。在我们的一个实验室中已经合成了以前出版的新颖系列的xanthen-3-one和xanthen-1,8-dione衍生物，它们在HeLa癌细胞系中显示出抗增殖活性。该系列为建立定量构效关系（QSAR），研究抗增殖活性与化学结构之间的关系提供了良好的基础。已推导了仅依赖于二维分子描述符的QSAR模型，从而提供了对x吨衍生物抗增殖活性的机械了解。该模型在内部和外部进行了验证，此外还使用了一组原始数据的非活性化合物，从而确认了模型在设计和发现新型x吨衍生物时的适用性。QSAR模型可从QsarDB存储库（http：//dx.doi.10.15152/QDB.237）获得。