Organometallic antitumour agents with alternative modes of action
The therapeutic index of drugs that target DNA, a ubiquitous target present in nearly all cells, is low. Nevertheless, DNA has remained the primary target for medicinal chemists developing metal-based anticancer drugs, although DNA has been essentially abandoned in favor of non-genomic targets by medicinal chemists developing org. drugs. A no. of organometallic drugs that target proteins/enzymes have been developed and these compds., based on ruthenium, osmium and gold, are described in this chapter. Targets include cathepsin B, thioredoxin reductases, multidrug resistance protein (Pgp), glutathione S-transferases and kinases. It is found that compds. that inhibit these various targets are active against metastatic tumors, or tumors that are resistant to classical DNA damaging agents such as cisplatin, and therefore offer considerable potential in clin. applications.
Keywords: Bioorganometallic chemistry ; Cancer chemotherapy ; Mode of action ; Organometallic compounds ; Protein binding ; Targeted drugs ; Dna-Binding Properties ; Mitochondrial Thioredoxin Reductase ; Ruthenium(Ii)-Arene Pta Complexes ; Lysosomal Cysteine Proteases ; Glutathione S-Transferases ; Vitro Anticancer Activity ; Human Serum-Albumin ; Spleen Cathepsin-B ; In-Vitro ; Gold(Iii) Complexes
Record created on 2010-12-14, modified on 2016-08-09