Huang Hung-Jin, Chetyrkina Margarita, Wong Chui-Wei, Kraevaya Olga A, Zhilenkov Alexander V, Voronov Ilya I, Wang Pei-Hwa, Troshin Pavel A, Hsu Shan-Hui
Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, ROC.
Skolkovo Institute of Science and Technology, Moscow, Russian Federation.
Comput Struct Biotechnol J. 2021 Jan 16;19:812-825. doi: 10.1016/j.csbj.2021.01.012. eCollection 2021.
Water-soluble fullerene derivatives are actively investigated as potential drugs for cancer treatment due to their favorable membranotropic properties. Herein, cytotoxic effects of twenty fullerene derivatives with different solubilizing addends were evaluated in three different types of non-small-cell lung carcinoma (NSCLC). The potential structural descriptors of the solubilizing addends related to the inhibitory activities on each type of lung cancer cell were investigated by the quantitative structure-activity relationship (QSAR) approach. The determination coefficient for the recommended QSAR model were 0.9325, 0.8404, and 0.9011 for A549, H460, and H1299 cell lines, respectively. The results revealed that the chemical features of the fullerene-based compounds including aromatic bonds, sulfur-containing aromatic rings, and oxygen atoms are favored properties and promote the inhibitory effects on H460 and H1299 cells. Particularly, thiophene moiety is the key functional group, which was positively correlated with strong inhibitory effects on the three types of lung cancer cells. The useful information obtained from our regression models may lead to the design of more efficient inhibitors of the three types of NSCLC.
水溶性富勒烯衍生物因其良好的膜亲和特性而作为潜在的癌症治疗药物受到积极研究。在此，评估了二十种带有不同增溶添加剂的富勒烯衍生物在三种不同类型的非小细胞肺癌（NSCLC）中的细胞毒性作用。通过定量构效关系（QSAR）方法研究了与每种类型肺癌细胞抑制活性相关的增溶添加剂的潜在结构描述符。推荐的QSAR模型对A549、H460和H1299细胞系的决定系数分别为0.9325、0.8404和0.9011。结果表明，基于富勒烯的化合物的化学特征，包括芳香键、含硫芳香环和氧原子，是有利的特性，并促进对H460和H1299细胞的抑制作用。特别是，噻吩部分是关键官能团，它与对三种类型肺癌细胞的强抑制作用呈正相关。从我们的回归模型中获得的有用信息可能会导致设计出更有效的三种类型NSCLC抑制剂。
