Recent Advances in Anticancer Copper Compounds

Andrew Kellett, Zara Molphy, Vickie McKee, Creina Slator

Publikation: Kapitel i bog/rapport/konference-proceedingKapitel i bogForskningpeer review

Abstrakt

There have been significant advances in the discovery of developmental copper complexes for the treatment of human cancer. The enzyme-active sites of several copper-containing enzymes suggest a starting point for metallodrug development and successful strategies have, so far, employed phenanthroline or bipyridine ligands to supply two pyridyl donors (modelling histidine residues) along with other oxygen or nitrogen donor ligands that tune specific properties. Suitably designed copper(ii) metallodrugs can generate reactive oxygen species (ROS) and reactive nitrogen species (RNS) that overwhelm innate cellular antioxidant defences to trigger oxidative damage and cell death. Recently, several complexes of this class were screened by the National Cancer Institute's (NCI) Developmental Therapeutics Program (DTP). The 60-cancer cell line screening results indicate copper(ii) metallodrug leads have unique activity and alternative mechanisms to clinically established anticancer agents such as cisplatin and bleomycin. Although DNA is a valid cellular target, mechanistic evidence suggests cell death is triggered by metal-catalysed pro-apoptotic ROS and RNS that damage cytoplasmic, mitochondrial, and genome function. In addition to copper complexes screened within the DTP, a number of other structurally relevant compounds are described, along with mechanistic aspects of their chemotherapeutic activity.

OriginalsprogEngelsk
TitelMetal-based Anticancer Agents
RedaktørerAnne Vessieres, Samuel M. Meier-Menches, Angela Casini
ForlagRoyal Society of Chemistry
Publikationsdato1. jan. 2019
Sider91-119
Kapitel4
ISBN (Trykt)978-1-78801-406-9
DOI
StatusUdgivet - 1. jan. 2019
NavnRSC Metallobiology
Nummer14
Vol/bind2019-January
ISSN2045-547X

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