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Met Ions Life Sci ; 182018 02 05.
Article in English | MEDLINE | ID: mdl-29394024

ABSTRACT

The general interest in anticancer metal-based drugs and some encouraging pharmacological results obtained at the beginning of the investigations on innovative Ru-based drugs triggered a lot of attention on NAMI-A and KP1019, the two Ru(III) coordination compounds that are the subject of this review. This great attention led to a considerable amount of scientific results and, more importantly, to their eventual admission into clinical trials. Both complexes share a relatively low systemic toxicity that allows reaching rather high dosages, comparable to those of carboplatin. Soon it became evident that NAMI-A and KP1019, in spite of their structural similarity, manifest very distinct chemical and biological properties. The pharmacological performances qualified KP1019 mainly as a cytotoxic drug for the treatment of platinum-resistant colorectal cancers, whereas NAMI-A gained the reputation of a potential anticancer drug with negligible effects on the primary tumor but a pronounced ability to affect metastases. We believe that a strictly comparative exam of NAMI-A and KP1019, based on the substantial body of studies accomplished since their discovery almost 30 years ago, might be an useful exercise, both for assessing the state of the art in terms of biological and clinical profiles, and of the inherent mechanisms, and for envisaging possible future developments in the light of past achievements.


Subject(s)
Antineoplastic Agents/pharmacology , Dimethyl Sulfoxide/analogs & derivatives , Drug Discovery/methods , Indazoles/pharmacology , Neoplasms/drug therapy , Organometallic Compounds/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/history , Antineoplastic Agents/metabolism , Cell Death/drug effects , Coordination Complexes , Dimethyl Sulfoxide/chemistry , Dimethyl Sulfoxide/history , Dimethyl Sulfoxide/metabolism , Dimethyl Sulfoxide/pharmacology , Drug Discovery/history , History, 20th Century , History, 21st Century , Humans , Indazoles/chemistry , Indazoles/history , Indazoles/metabolism , Models, Molecular , Molecular Structure , Neoplasms/history , Neoplasms/metabolism , Neoplasms/pathology , Organometallic Compounds/chemistry , Organometallic Compounds/history , Organometallic Compounds/metabolism , Protein Binding , Ruthenium Compounds , Structure-Activity Relationship , Tissue Distribution
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