Metal complexes having dual histone deacetylase inhibitory and DNA-binding activity

摘要

Compounds comprising a metal complex having the structure [X—Y—Z-Mn+]p+.B are disclosed in which X is a histone deacetylase inhibitor, Mn+ is a DNA-binding heavy metal ion, Y is an aliphatic or aromatic spacer or is absent, and Z is a mono- or bi-dentate or chelating donor linker, or a bridging linker, P+ designates the charge on the complex ion, which may be positive, negative or absent and B is a counterion or is absent. The linker Z is labile and its metal complex X—Y—Z-Mn+ is capable of being hydrolysed in-vivo. The compounds find application in the treatment of cancer.

主权项

1. A metal complex comprising a histone deacetylase (HDAC) inhibitor coordinated to a DNA-binding heavy metal ion and having the general structure:
[X—Y—Z-Mn+]P+.B in which:
X is a HDAC inhibitor having a terminal hydroxamate group;Y is a spacer group or is absent;Z is a mono-dentate, bi-dentate, bridging or chelating oxygen donor linker;Mn+ is a DNA-binding heavy metal ion selected from platinum, palladium, ruthenium, osmium, gold, iron and copper, in which the heavy metal ion is coordinated to one or more ligands to complete its coordination sphere;P+ designates the charge on the complex ion, which may be positive, negative or absent; andB is a counterion or is absent.