Author/Authors :
Alex W. White، نويسنده , , Nicola J. Curtin، نويسنده , , Brian W. Eastman، نويسنده , , Bernard T. Golding، نويسنده , , Zdenek Hostomsky، نويسنده , , Suzanne Kyle، نويسنده , , Jianke Li، نويسنده , , Karen A. Maegley، نويسنده , , Donald J. Skalitzky، نويسنده , , Stephen E. Webber، نويسنده , , Xiaohong Yu، نويسنده , , Roger J. Griffin، نويسنده ,
Abstract :
The synthesis and biological evaluation of a new series of amine-substituted 2-arylbenzimidazole-4-carboxamide inhibitors of the DNA-repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1) is reported. The introduction of an amine substituent at the 2-aryl position is not detrimental to activity, with most inhibitors exhibiting Ki values for PARP-1 inhibition in the low nanomolar range. Two compounds in this series were found to potentiate the cytotoxicity of the DNA-methylating agent temozolomide by 4–5-fold in a human colorectal cancer cell line.
Keywords :
inhibitors , Benzimidazole-4-carboxamides , Chemopotentiation. , PARP-1
