Biological activity of water-soluble fullerenes. Structural dependence of DNA cleavage, cytotoxicity, and enzyme inhibitory activities including HIV-protease inhibition

被引:184
作者
Nakamura, E
Tokuyama, H
Yamago, S
Shiraki, T
Sugiura, Y
机构
[1] UNIV TOKYO, FAC PHARMACEUT SCI, BUNKYO KU, TOKYO 113, JAPAN
[2] KYOTO UNIV, DEPT SYNTHET CHEM & BIOL CHEM, SAKYO KU, KYOTO 60601, JAPAN
[3] KYOTO UNIV, INST CHEM RES, UJI, KYOTO 611, JAPAN
关键词
D O I
10.1246/bcsj.69.2143
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Two different classes of water-soluble fullerene derivatives, detergent-type and sphere-type, were synthesized. The derivatives were evaluated for their biological activities including cytotoxicity, DNA cleavage, and inhibition of HIV-protease and other enzymes. Both classes of compounds display generally similar behavior except for their cytotoxicity spectra against several cell lines. The fullerene derivatives bearing N-methylpyrrole were found to be photo-inactive with respect to DNA cleaving activity and cytotoxicity. A study on the kinetics for the inhibition of HIV-protease with detergent type derivative revealed that the compound is a potent fullerene-based HIV protease inhibitor, inhibiting the enzyme activity in a reversible and competitive manner with a K-i value of 0.32 mu M.
引用
收藏
页码:2143 / 2151
页数:9
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