Organometallic Anticancer Compounds
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The quest for alternative drugs to the well-known cisplatin and its derivatives, which are still used in more than 50% of the treatment regimes for patients suffering from cancer, is highly needed, and organometallic compounds have recently been found to be promising anticancer drug candidates.Abstract:
The quest for alternative drugs to the well-known cisplatin and its derivatives, which are still used in more than 50% of the treatment regimes for patients suffering from cancer, is highly needed.1,2 Despite their tremendous success, these platinum compounds suffer from two main disadvantages: they are inefficient against platinum-resistant tumors, and they have severe side effects such as nephrotoxicity. The latter drawback is the consequence of the fact that the ultimate target of these drugs is ubiquitous: It is generally accepted that Pt anticancer drugs target DNA, which is present in all cells.3,4 Furthermore, as a consequence of its particular chemical structure, cisplatin in particular offers little possibility for rational improvements to increase its tumor specificity and thereby reduce undesired side effects.
In this context, organometallic compounds, which are defined as metal complexes containing at least one direct, covalent metal−carbon bond, have recently been found to be promising anticancer drug candidates. Organometallics have a great structural variety (ranging from linear to octahedral and even beyond), have far more diverse stereochemistry than organic compounds (for an octahedral complex with six different ligands, 30 stereoisomers exist!), and by rational ligand design, provide control over key kinetic properties (such as hydrolysis rate of ligands). Furthermore, they are kinetically stable, usually uncharged, and relatively lipophilic and their metal atom is in a low oxidation state. Because of these fundamental differences compared to “classical coordination metal complexes”, organometallics offer ample opportunities in the design of novel classes of medicinal compounds, potentially with new metal-specific modes of action. Interestingly, all the typical classes of organometallics such as metallocenes, half-sandwich, carbene-, CO-, or π-ligands, which have been widely used for catalysis or biosensing purposes, have now also found application in medicinal chemistry (see Figure Figure11 for an overview of these typical classes of organometallics).
Figure 1
Summary of the typical classes of organometallic compounds used in medicinal chemistry.
In this Perspective, we report on the recent advances in the discovery of organometallics with proven antiproliferative activity. We are emphasizing those compounds where efforts have been made to identify their molecular target and mode of action by biochemical or cell biology studies. This Perspective covers more classes of compounds and in more detail than a recent tutorial review by Hartinger and Dyson.(5) Furthermore, whereas recent reviews and book contributions attest to the rapid development of bioorganometallic chemistry in general,6,7 this Perspective focuses on their potential application as anticancer chemotherapeutics. Another very recent review article categorizes inorganic anticancer drug candidates by their modes of action.(8) It should be mentioned that a full description of all currently investigated types of compounds is hardly possible anymore in a concise review. For example, a particularly promising class of organometallic anticancer compounds, namely, radiolabeled organometallics, has been omitted for space limitations. Recent developments of such compounds have been reviewed in detail by Alberto.(9)read more
Citations
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Organometallic Ruthenium and Iridium Transfer‐Hydrogenation Catalysts Using Coenzyme NADH as a Cofactor
Soledad Betanzos-Lara,Zhe Liu,Abraha Habtemariam,Ana M. Pizarro,Bushra Qamar,Peter J. Sadler +5 more
TL;DR: Artificial enzymes: half-sandwich arene ruthenium(II) and cyclopentadienyl iridium(III) complexes containing N,N-chelated ligands can use NADH as a source of hydride for the reduction of ketones to raise the NAD(+)/NADH ratio in cancer cells.
Journal ArticleDOI
Towards cancer cell-specific phototoxic organometallic rhenium(I) complexes
TL;DR: Fluorescent microscopy on cervical cancer cells (HeLa) showed that the conjugation of Re-COOH to NLS significantly enhanced the compound's accumulation into the cell nucleus and more specifically into its nucleoli.
Journal ArticleDOI
DNA Binding and Anti-Cancer Activity of Redox-Active Heteroleptic Piano-Stool Ru(II), Rh(III), and Ir(III) Complexes Containing 4-(2-Methoxypyridyl)phenyldipyrromethene
Rakesh Kumar Gupta,Rampal Pandey,Gunjan Sharma,Ritika Prasad,Biplob Koch,Saripella Srikrishna,Pei-Zhou Li,Qiang Xu,Daya Shankar Pandey +8 more
TL;DR: The results suggest that in vitro antitumor activity of 1-4 lies in the order 2 > 1 > 4 > 3.
Journal ArticleDOI
DNA/protein binding, molecular docking, and in vitro anticancer activity of some thioether-dipyrrinato complexes.
Rakesh Kumar Gupta,Gunjan Sharma,Rampal Pandey,Amit Kumar,Biplob Koch,Pei-Zhou Li,Qiang Xu,Daya Shankar Pandey +7 more
TL;DR: A remarkable decrease in the in vitro DL cell proliferation and induction of the apoptosis by 1-4 is revealed, which lies in the order 2 > 1 > 4 > 3.
Journal ArticleDOI
Metallopolymers with transition metals in the side-chain by living and controlled polymerization techniques
TL;DR: In this article, a summary of side-chain transition metal-containing polymers prepared by controlled and living polymerizations is summarized. But the work on side-chains transition metal polymers is limited to metal carbonyl complex polymers.
References
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Journal ArticleDOI
Inflammation and cancer
Lisa M. Coussens,Zena Werb +1 more
TL;DR: It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration.
Journal ArticleDOI
Cellular processing of platinum anticancer drugs.
Dong Wang,Stephen J. Lippard +1 more
TL;DR: This review focuses on recently discovered cellular pathways that are activated in response to cisplatin, including those involved in regulating drug uptake, the signalling of DNA damage, cell-cycle checkpoints and arrest, DNA repair and cell death.
BookDOI
Cisplatin : chemistry and biochemistry of a leading anticancer drug
TL;DR: The start: platinum complexes for the treatment of cancer - why the search goes on and new developments: structure-activity relationships within di- and trinuclear platinum phase I clinical anticancer agents the development of orally-active platinum drugs methods for screening the potential antitumor activity of platinum compounds in combinatorial libraries computational studies on platinum antitumors complexes and their adducts with nucleid acids constituents.
Journal ArticleDOI
Bioorganometallic Chemistry of Ferrocene
Journal ArticleDOI
Bioorganometallic chemistry—from teaching paradigms to medicinal applications
TL;DR: In this tutorial review, various aspects of bioorganometallic chemistry are introduced, with the main emphasis on medicinal organometallic compounds, and rational ligand design has been shown.