Synthesis and antitumor activity of novel pyridinium fullerene derivatives
| Autor: | Kyoko Takahashi, Shigeo Nakamura, Tomoyuki Ohe, Takumi Yasuno, Hitomi Ikeda, Tadahiko Mashino |
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| Rok vydání: | 2019 |
| Předmět: |
Stereochemistry
Biophysics Substituent Pharmaceutical Science Bioengineering 02 engineering and technology 010402 general chemistry medicine.disease_cause 01 natural sciences Biomaterials chemistry.chemical_compound In vivo Drug Discovery Structural isomer medicine P-glycoprotein biology Organic Chemistry General Medicine 021001 nanoscience & nanotechnology 0104 chemical sciences chemistry biology.protein Pyridinium 0210 nano-technology Lead compound Intracellular Oxidative stress |
| Zdroj: | International Journal of Nanomedicine. 14:6325-6337 |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s212045 |
| Popis: | Purpose We have previously reported that some cationic fullerene derivatives exhibited anticancer activity, and they are expected to be a potential lead compound for an anti-drug resistant cancer agent. However, they are bis-adducts and a mixture of multiple regioisomers, which cannot be readily separated due to the variability of substituent positions on the fullerene cage. To overcome this issue, we evaluated the antiproliferative activities of a set of mono-adduct derivatives and examined their structure-activity relationship. In addition, the in vivo antitumor activity of selected derivatives was also examined. Methods Nineteen pyridinium fullerene derivatives were newly designed and synthesized in this study. Their antiproliferative activities were evaluated using several cancer cell lines including drug-resistant cells. Furthermore, in vivo antitumor activity of several derivatives was investigated in mouse xenograft model of human lung cancer. Results The derivatives inhibited the proliferation of cancer cell lines, including cisplatin-resistant cells and doxorubicin-resistant cells. It was also shown that compound 10 (10 μM), 13 (10 μM) and cis-14 (10 μM) induced the intracellular oxidative stress. In addition, compound 13 (20 mg/kg) and cis-14 (15 mg/kg) significantly exhibited antitumor activity in mouse xenograft model of human lung cancer. Conclusion We synthesized a novel set of mono-adduct fullerene derivatives functionalized with pyridinium groups and found that most of them show potent antiproliferative activities against cancer cell lines and some of them show significant antitumor activities in vivo. We propose that these fullerene derivatives serve as the lead compounds for a novel type of antitumor agents. |
| Databáze: | OpenAIRE |
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