Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy

Abstract

The introduction of biologically relevant organic moieties in the coordination sphere of transition metal complexes has recently become a well-established strategy to increase the selectivity and biocompatibility of metallodrugs. In this review, the major advances achieved in this area of research in the last three years are described in detail. Particular attention is given to the metal complexes bearing the main biomolecules of life: carbohydrates, lipids, nucleotides, proteins and vitamins. Each paragraph summarizes the synthetic strategy employed to obtain the complexes of interest as well as the most interesting biological results obtained with these potential metallodrugs. Moreover, the structure–activity relationships observed by the different research groups are described and discussed, with the goal of suggesting to the reader the ligand/metal centre combinations that provide the most promising results in the fight against cancer. Some of the compounds examined in this review as well as other bioconjugated metal complexes published in recent decades exhibit interesting selectivity towards cancer cells over normal ones and a specific mode of action. These latter aspects are the basis of what is commonly known as anticancer target therapy.

Synergistic applications of cyclodextrin-based systems and metal–organic frameworks in transdermal drug delivery for skin cancer therapy

“…The most common approach involves the conjugation of target molecules such as specific proteins, nucleotides or antibodies on the surface of nanoparticles containing therapeutic compound. 85,86 Another approach, known as passive targeting, is based on the greater permeability of tumor cells compared to healthy ones (EPR effect). 87…”

Dinuclear NHC–gold(i)–thiolato and –alkynyl complexes: synthesis, anticancer activity, and catalytic activity in lactonization reactions

“…In the last decades, due to various side-effects exhibited by platinum-based anticancer drugs, 1–3 much research has focused on the exploration of the potential anticancer properties of other metal complexes bearing a wide range of organic ligands. 4,5 Encouragingly, some gold, 6–11 ruthenium 12,13 and palladium 14–17 complexes have shown excellent in vitro , ex vivo and in vivo antitumor activity. More importantly, these not only proceed via a completely different mechanism of action from conventional platinum drugs, but they are often effective against cisplatin-resistant cancer cells, 18 a fact that has attracted a great deal of attention.…”

“…Mononuclear gold( i ) complexes are of importance in medicinal chemistry as they can be used for the treatment of rheumatic diseases, 19 but they have also great potential as antibiotics and chemotherapeutic agents. 7,8 Intensive studies in recent decades have demonstrated that anticancer gold complexes have a wide range of cellular targets, such as mitochondria and specific proteins that exert relevant functional roles ( e.g. thioredoxin reductase (TrxR), poly(ADP-ribose) polymerase (PARP-1), chelating proteins, proteasome, and protein tyrosine phosphatases).…”

Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

“…In this work, we present the synthesis, characterization, and evaluation of the anticancer potential of a novel series of diruthenium complexes derived from [Ru 2 Cp 2 (CO) 4 ] via the incorporation of alkynes, including two estradiol-containing alkynes. It has to be remarked that tethering a bioactive molecule to an anticancer metal scaffold is a prominent approach to optimize the performance of the complex. − This field of research has included the conjugation of metal structures with, inter alia, steroid hormone derivatives, and related examples have appeared in the literature concerning platinum­(II), , ferrocene, and ruthenium arene complexes . Steroidal units may enhance the antiproliferative activity especially against hormone-dependent cancer cells (e.g., breast cancer cells), by facilitating the intracellular drug uptake through steroid receptor systems …”