Details

Autor(en) / Beteiligte

• Yasuno, Takumi
• Ohe, Tomoyuki
• Ikeda, Hitomi
• Takahashi, Kyoko
• Nakamura, Shigeo
• Mashino, Tadahiko

Titel

Synthesis and antitumor activity of novel pyridinium fullerene derivatives

Ist Teil von

• International journal of nanomedicine, 2019-08, Vol.14, p.6325-6337

Ort / Verlag

New Zealand: Dove Medical Press Limited

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• 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. 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. The derivatives inhibited the proliferation of cancer cell lines, including cisplatin-resistant cells and doxorubicin-resistant cells. It was also shown that compound (10 μM), (10 μM) and - (10 μM) induced the intracellular oxidative stress. In addition, compound (20 mg/kg) and - (15 mg/kg) significantly exhibited antitumor activity in mouse xenograft model of human lung cancer. 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.