Efremova Anna S, Zakharenko Alexandra L, Shram Stanislav I, Kulikova Irina V, Drenichev Mikhail S, Sukhanova Maria V, Khodyreva Svetlana N, Myasoedov Nikolay F, Lavrik Olga I, Mikhailov Sergey N
a Institute of Molecular Genetics , Russian Academy of Sciences , Moscow , Russia.
Nucleosides Nucleotides Nucleic Acids. 2013;32(9):510-28. doi: 10.1080/15257770.2013.827793.
Nearly 30 synthetic nucleosides were tested with human recombinant poly(ADP-ribose) polymerase 1 as potential inhibitors of this enzyme. The most active compounds were some disaccharide analogues of thymidine: 3'-O-β-D-ribofuranosyl-5-iodo-dUrd (2d; IC₅₀ = 45 μM), 3'-O-β-D-ribofuranosyl-2'-deoxythymidine (2e; IC₅₀ = 38 μM), and 3'-O-β-D-ribofuranosyl-2'-deoxythymidine oxidized (4; IC₅₀ = 25 μM). These compounds also reduced H₂O₂-induced synthesis of poly(ADP-ribose) in cultured human ovarian carcinoma (SKOV-3) cells in a dose-dependent manner. Furthermore, compounds 2d or 2e until a concentration of 1 mM did not affect growth of SKOV-3 cells, whereas dialdehyde compound 4, as well as thymidine, exhibited a significant cytotoxicity.
将近30种合成核苷作为该酶的潜在抑制剂，用重组人聚（ADP - 核糖）聚合酶1进行了测试。活性最高的化合物是一些胸苷的二糖类似物：3'-O-β-D-呋喃核糖基-5-碘-dUrd（2d；IC₅₀ = 45 μM）、3'-O-β-D-呋喃核糖基-2'-脱氧胸苷（2e；IC₅₀ = 38 μM）以及氧化的3'-O-β-D-呋喃核糖基-2'-脱氧胸苷（4；IC₅₀ = 25 μM）。这些化合物还以剂量依赖的方式降低了培养的人卵巢癌细胞（SKOV - 3）中H₂O₂诱导的聚（ADP - 核糖）合成。此外，在浓度达到1 mM之前，化合物2d或2e不影响SKOV - 3细胞的生长，而二醛化合物4以及胸苷则表现出显著的细胞毒性。
