Novel Metals and Metal Complexes as Platforms for Cancer Therapy

Abstract

Metals are essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. The use of metals and their salts for medicinal purposes, from iatrochemistry to modern day, has been present throughout human history. The discovery of cisplatin, cis-[PtII(NH3)2Cl2], was a defining moment which triggered the interest in platinum(II)- and other metal-containing complexes as potential novel anticancer drugs. Other interests in this field address concerns for uptake, toxicity, and resistance to metallodrugs. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. The use of nonessential metals as probes to target molecular pathways as anticancer agents is also emphasized. Finally, based on the interface between molecular biology and bioinorganic chemistry the design of coordination complexes for cancer treatment is reviewed and design strategies and mechanisms of action are discussed.

Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

“…Although clinical response rates to Pt drugs can exceed 60% in late stage patients, relapse and the subsequent development of resistance leads to treatment failure and low survival rates. As such, there is much interest in the discovery of new metal-based drugs with alternative target sites and mechanisms of action (MOA) to which resistance cannot readily develop (1)(2)(3)(4)(5)(6). Osmium, also a third-row transition metal, offers promise for distinct metal-based anticancer agents (7).…”

Binding Behavior of Few Lanthanides and Heavy Metal ions with Proteins by Fast and Reliable Affinity Capillary Electrophoresis Method

“…selenium on glutathione peroxidase. Furthermore, Cu 2+ , Mn 2+ , Fe 2+ and Ni 2+ can be incorporated to form active sites of antioxidant defense enzymes such as superoxide dismutases and Mg can be incorporated for hexokinase 3-5. The toxicity of some of the heavy metals such as Hg 2+ and As 3+ can be manifested when they bind irreversibly to a variety of selenocystine enzymes [6][7][8]. The investigation of diagnostic biomarkers for several diseases such as metalloproteins is still growing 1. Furthermore, a substantial progress in producing organometallic complexes for several disorders such as cancer, inflammation, infection and neurological disorders have been achieved [9][10][11] .…”

Kuersetinin Cu(II) ve Al(III) Komplekslerinin Potansiyometrik ve Kromatografik İncelenmesi

“…In recent years, metal−organic complexes have drawn much attention because many organic molecules can coordinate with various metal ions to form metal complexes with diverse geometries, providing infinite possibilities for coordination numbers and applications (6,7). The widespread success of cisplatin in the clinical treatment of various types of tumor has placed coordination chemistry of metal-based drugs in the frontline in the fight against cancer.…”