Hung-Jin Huang1,2, Olga A Kraevaya3,4, Ilya I Voronov4, Pavel A Troshin3,4, Shan-Hui Hsu1,2,5. 1. Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan. 2. Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan. 3. Skolkovo Institute of Science and Technology, Moscow, Russian Federation. 4. Institute for Problems of Chemical Physics of Russian Academy of Sciences, Chernogolovka, Russian Federation. 5. Research and Development Center for Medical Devices, National Taiwan University, Taipei, Taiwan.
Abstract
BACKGROUND: Nanotechnology-based strategies in the treatment of cancer have potential advantages because of the favorable delivery of nanoparticles into tumors through porous vasculature. MATERIALS AND METHODS: 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. RESULTS: In the QSAR regression model, the evaluation results revealed that the determination coefficient r2 and leave-one-out cross-validation q2 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. CONCLUSION: 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.
BACKGROUND: Nanotechnology-based strategies in the treatment of cancer have potential advantages because of the favorable delivery of nanoparticles into tumors through porous vasculature. MATERIALS AND METHODS: 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. RESULTS: In the QSAR regression model, the evaluation results revealed that the determination coefficient r2 and leave-one-out cross-validation q2 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. CONCLUSION: 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.
Authors: Alessio De Simone; Debora Russo; Gian Filippo Ruda; Alessandra Micoli; Mariarosaria Ferraro; Rita Maria Concetta Di Martino; Giuliana Ottonello; Maria Summa; Andrea Armirotti; Tiziano Bandiera; Andrea Cavalli; Giovanni Bottegoni Journal: J Med Chem Date: 2017-03-02 Impact factor: 7.446
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