DISACCHARIDE PYRIMIDINE NUCLEOSIDES AND THEIR DERIVATIVES: A NOVEL GROUP OF CELL-PENETRATING INHIBITORS OF POLY(ADP-RIBOSE) POLYMERASE 1

作者：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^*

来源：Nucleosides Nucleotides & Nucleic Acids, 2013, 32(9): 510-528.

DOI：10.1080/15257770.2013.827793

• Disaccharide pyrimidine nucleosides
• poly(ADP-ribose) polymerase 1 inhibitors
• DNA repair
• cytotoxicity
• SKOV-3 human ovarian carcinoma cell line

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-beta-D-ribofuranosyl-5-iodo-dUrd (2d; IC50 = 45 mu M), 3-O-beta-D-ribofuranosyl-2-deoxythymidine (2e; IC50 = 38M), and 3-O-beta-D-ribofuranosyl-2-deoxythymidine oxidized (4; IC50 = 25 mu M). 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 1mM did not affect growth of SKOV-3 cells, whereas dialdehyde compound 4, as well as thymidine, exhibited a significant cytotoxicity.

• 出版日期2013-9-2