Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan.
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
Int J Nanomedicine. 2020 Apr 14;15:2485-2499. doi: 10.2147/IJN.S243463. eCollection 2020.
Nanotechnology-based strategies in the treatment of cancer have potential advantages because of the favorable delivery of nanoparticles into tumors through porous vasculature.
In the current study, we synthesized a series of water-soluble fullerene derivatives and observed their anti-tumor effects on human lung carcinoma A549 cell lines. The quantitative structure-activity relationship (QSAR) modeling was employed to investigate the relationship between anticancer effects and descriptors relevant to peculiarities of molecular structures of fullerene derivatives.
In the QSAR regression model, the evaluation results revealed that the determination coefficient and leave-one-out cross-validation for the recommended QSAR model were 0.9966 and 0.9246, respectively, indicating the reliability of the results. The molecular modeling showed that the lack of chlorine atom and a lower number of aliphatic single bonds in saturated hydrocarbon chains may be positively correlated with the lung cancer cytotoxicity of fullerene derivatives. Synthesized water-soluble fullerene derivatives have potential functional groups to inhibit the proliferation of lung cancer cells.
The guidelines obtained from the QSAR model might strongly facilitate the rational design of potential fullerene-based drug candidates for lung cancer therapy in the future.
基于纳米技术的癌症治疗策略具有潜在优势，因为纳米粒子可以通过多孔血管系统有利地递送到肿瘤中。
在本研究中，我们合成了一系列水溶性富勒烯衍生物，并观察了它们对人肺癌 A549 细胞系的抗肿瘤作用。采用定量构效关系（QSAR）建模来研究抗癌作用与与富勒烯衍生物分子结构特征相关描述符之间的关系。
在 QSAR 回归模型中，推荐的 QSAR 模型的确定系数 和留一交叉验证 分别为 0.9966 和 0.9246，表明结果的可靠性。分子建模表明，缺乏氯原子和饱和烃链中脂肪单键数量较少可能与富勒烯衍生物的肺癌细胞毒性呈正相关。合成的水溶性富勒烯衍生物具有抑制肺癌细胞增殖的潜在功能基团。
从 QSAR 模型中获得的指导原则可能会极大地促进未来基于富勒烯的潜在药物候选物用于肺癌治疗的合理设计。
