Novel Coordination Complexes of a Few Essential Trace Metals: Cytotoxic Properties and Lead Identification for Drug Development for Cancer

Abstract

Metals and metal compounds have been used in medicine since ancient times. Transition metals, which exhibit different oxidation states and can interact with biomolecules, have an important place in the field of medicinal chemistry. This property of transition metals facilitated the development of metal-based drugs with promising pharmacological applications and unique therapeutic opportunities. Discovery of antitumor activity of a transition metal complex, cis-diamminedichloroplatinum(II) (cisplatin), during the 1960s has been a milestone in metal-based cancer chemotherapeutics and provided leads for the synthesis of many more transition metal complexes for treatment of cancer. In our laboratories, we synthesize, isolate, and characterize transition metal coordination complexes such as iron(II), cobalt(II), nickel(II), and copper(II), which are all among the essential metals and so could be potentially producing little or less side effects, and study the DNA-binding and cytotoxic properties of the complexes. Some of these complexes, in view of their unique mode of binding with DNA, were found to affect the viability of cancer cells by bringing about specific modes of cell death, namely, apoptosis, necrosis, and/or necroptosis, with or without generation of reactive oxygen species. This review summarizes the salient outcomes of our systematic study and the potential leads these cytotoxic complexes provide.