Metal Anticancer Complexes – Activity, Mechanism of Action, Future Perspectives

Abstract

Cisplatin was first administered to a cancer patient in 1971 and obtained FDA approval for general oncology practice in 1978. [1] These events opened the way to the thriving of medicinal inorganic chemistry, a sub-discipline that traditionally -for historical reasons -has been mainly focused on cancer. This cluster issue of the European Journal of Inorganic Chemistry, with 31 contributions from scientists from all over the world, provides an excellent updated picture of the field. To the Guest Editors of this issue, who have been involved in anticancer metal compounds since the time they were fellow Ph. D. students in Italy more than 30 years ago, some general trendsthe "future perspectives" explicitly mentioned in the title of the issue -appear very clearly. They are listed below, in an order that does not necessarily reflect their importance.In general, we notice that there is an increasing number of examples -distributed in many review and research papersconcerning structural metal compounds that have anticancer activity (at least in vitro), i.e. compounds that are coordinatively saturated and inert. Structural compounds have no labile ligands that might open up coordination positions, and thus the metal is not expected to bind directly to any biological target, be it to DNA, a protein (e.g. in a signaling pathway), an extracellular component, etc. [2] For decades, such compounds -in which the role of the metal is that of determining the 3D shape of the compound and/or to start an electron-transfer processhad been regarded as useless for medicinal applications. Another important trend that is clearly emerging from this cluster issue concerns the increasing focus on molecularly targeted metal compounds, both for cancer treatment and diagnosis. Two Microreviews, presented by Ulrich Bierbach, Luca Ronconi and their coworkers, and some of the other contributions deal with this topic. These two trends are intimately connected and strictly related to the identification of new targets -aside from DNA -and new mechanisms of action that are peculiar to transition-metal compounds. Remarkably, the Essay by Peter Sadler [a]

Cytotoxic performances of new anionic cyclometalated Pt(II) complexes bearing chelated O^O ligands

“…Owing to the numerous side effects, long‐term resistance and clinical limitations of the well‐known first‐generation Pt(II) anticancer complex cisplatin (Chart 1a), numerous DNA‐binding platinum drugs have been developed over the years . The so‐called second‐generation platinum drugs include Pt(II) complexes which deviate from the cisplatin template as the metal centre experiences a different ligand field, leading to a modulation of the electronic, steric hindrance and basicity features .…”

New Findings in Metal Complexes with Antiproliferative Activity Containing 1,3,5‐Triaza‐7‐phosphaadamantane (PTA) and Derivative Ligands

“…[4][5][6] Coordination compounds with metals other than platinum, particularly ruthenium(II)-based complexes, are emerging as promising antiproliferative and antimetastatic agents with potential uses. Since FDA approval in 1978, cisplatin, [7][8][9][10] has been used in medical cancer treatment, which is notable as it was the first transition metal complex found to have anticancer activity. It is also worth to stress that cisplatin is effective against cancers such as sarcomas, carcinomas (small cell lung and ovarian cancer), lymphomas, and germ cell tumours.…”

CpRu Complexes Containing Water Soluble Phosphane PTA and Natural Purines Adenine, Guanine and Theophylline: Synthesis, Characterization, and Antiproliferative Properties

“…After the discovery of the anticancer properties of cis platin in the sixties by Rosenberg, a huge number of metal derivatives have been synthesized and tested as therapeutic agents for cancer treatment . Although the use of cis platin and its analogues present important secondary effects, they are still some of most widely used chemotherapeutic agents up to date . To overcome the drawbacks associated to the platinum drugs, the research on metal complexes bearing different metals is a topic of primary interest .…”

“…[2][3][4][5][6][7][8][9][10] Although the use of cisplatin and its analogues present important secondary effects, [11][12][13][14][15][16][17] they are still some of most widely used chemotherapeutic agents up to date. [18][19][20][21][22] To overcome the drawbacks associated to the platinum drugs, the research on metal complexes bearing different metals is a topic of primary interest. [23][24][25][26][27][28][29] Among the non-platinum cytotoxic complexes those containing ruthenium are the most promising.…”