Partners and International Organizations
(English)
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AT, BE, CH, CZ, DE, DK, ES, FR, GR, HU, IE, IL, IT, NL, NO, PL, PT, RO, SE, SI, TR, UK
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Abstract
(English)
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The reactions of anticancer metallodrugs with proteins/enzymes are attracting increasing attention as it is now evident that proteins may constitute realistic major targets for this class of pharmacological agents. The proposed project aims at investigating the interactions of metal-based anticancer drugs with proteins in vitro using an integrated approach that includes several biophysical/biochemical methods coupled to enzyme inhibition and pharmacological assays. The obtained information has provided knowledge on the possible mechanisms of action of various families of metal-based anticancer agents, mainly based on platinum, ruthenium and gold. In particular gold complexes have shown favorable cytotoxic properties on a panel of human cancer cell lines, as well as promising enzyme inhibition proterties. During the project duration both cytotoxic platinum complexes and antimetastatic ruthenium compounds have also been characterized for their interactions with some relevant protein targets such as cathepsins and carbonic anhydrases. In some cases, specific pharmacological assays to evaluate the antimetastatic properties of metallodrugs in vitro and in vivo have been developed. Remarkably, for the first time the inhibition by metal compounds of the zinc-finger protein PARP-1, with a role in the development of cancer resistance to chemotherapy, has been reported.
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