Mashino Tadahiko
Faculty of Pharmacy, Keio University.
Yakugaku Zasshi. 2022;142(2):165-179. doi: 10.1248/yakushi.21-00188.
Fullerene (C) and fullerene derivatives are attractive novel compounds not only for carbon materials of nanotechnology but also for medical fields because of its unique chemical and physical properties. We intend to develop fullerene derivatives as novel lead compounds for drug discovery. At first, we synthesized many types of water-soluble fullerene derivatives to investigate their biological activities because of their poor solubility in water. We found that anionic fullerene derivatives possess anti-oxidant activities, whereas di-cationic fullerene derivatives exhibited antiproliferative activities against various cancer cell lines including drug-resistant cells. Proline-type fullerene derivatives showed inhibitory activities against human immunodeficiency virus (HIV) reverse transcriptase, HIV protease, hepatitis C virus (HCV) NS5B RNA polymerase, and HCV NS3/4A protease. These activities may strongly inhibit virus replication via a synergistic effect and fullerene derivatives may be used as novel multi-target drugs for the treatment of AIDS and hepatitis C in the future.
富勒烯（C）及其衍生物不仅因其独特的化学和物理性质，对纳米技术的碳材料具有吸引力，而且在医学领域也备受关注。我们打算开发富勒烯衍生物作为药物发现的新型先导化合物。首先，由于富勒烯在水中的溶解度较差，我们合成了多种水溶性富勒烯衍生物以研究其生物活性。我们发现阴离子型富勒烯衍生物具有抗氧化活性，而双阳离子型富勒烯衍生物对包括耐药细胞在内的多种癌细胞系表现出抗增殖活性。脯氨酸型富勒烯衍生物对人类免疫缺陷病毒（HIV）逆转录酶、HIV蛋白酶、丙型肝炎病毒（HCV）NS5B RNA聚合酶和HCV NS3/4A蛋白酶具有抑制活性。这些活性可能通过协同作用强烈抑制病毒复制，富勒烯衍生物未来可能用作治疗艾滋病和丙型肝炎的新型多靶点药物。
