Coordination complexes are a promising platform for design of new drugs, due to their structural versatility and potential application as pharmacological alternatives. Due to its pharmacodynamic properties, bioavailability enhancement, and toxicity decrease of certain metal ions, it has been widely used as a therapeutic compound for the treatment of a wide range of human diseases, most commonly cancer. In addition to this, the complexes have shown great potential for applications in the diabetes, inflammation, and bacterial infections fields.
Advantages
Coordination complexes offer many advantages in the development of new drugs. The main advantages are as follows:
1. Coordination complexes offer a rich environment to build upon a variety of distinct molecular structures that confer a wide spectrum of coordination numbers and geometries, as well as kinetic properties. This makes it possible to create a wide range of drugs.
2. The oxidation state of a metal is important for the coordination compounds, given that it allows the participation in biological redox chemistry and plays an influential role in optimal dose and bioavailability of the agent administered.
3. The partially filled d orbitals in transition metals impart interesting electronic properties that can act as suitable probes in the design of anti-disease agents.
Application
Many coordination complexes have been utilized throughout history to treat a wide variety of diseases. These diseases include cancer, diabetes, inflammation, and bacterial infections. Specific examples of the use of coordination complexes for disease treatment are shown below.
➢ Treatment of cancer
Diamminedichloroplatinum (II) is a complex with square planar geometry and two possible cis and trans geometrical isomers, cisplatin and transplatin.
Cisplatin has been a first-line therapy in many cancers and nowadays is used either alone or in combination with other compounds in many cancers, e.g., testicular, ovarian or bladder cancers or leukaemias. In contrast to cisplatin, the trans isomer of the diamminedichloroplatinum (II), transplatin, shows only mild cytotoxic activity.
Figure 1. Structures of the cis (a) and trans (b) isomers of diamminedichloroplatinum (II), the cisplatin and transplatin, respectively.
Complexes of Pt (IV) are thermodynamically stable, kinetically inert, and diamagnetic. The metal ion is hexa-coordinated and its complexes have octahedral geometry. The biological properties of such complexes can be finely tuned thanks to the six coordination sites available. Despite some disagreement, it is now generally accepted that the antitumor activity of Pt (IV) complexes is due to their reduction to Pt (II) analogs. The most prominent example from this group is satraplatin, an octhahedral pt (IV) complex that is administered orally and is currently in advanced clinical stages for treatment of hormone refractory prostate cancer.
➢ Treatment of other diseases
- Vanadium complexes in treatment of diabetes
Despite the reluctance to believe, diabetes mellitus continues to remain one of major reasons for mortality and morbidity rate all over the globe. Although injected insulin can alleviate many of the symptoms in an intermittent fashion, there is no simple cure that restores glucose homeostasis around the clock. The discovery, in 1985, that a simple vanadium salt, sodium orthovanadate, added to drinking water, could reverse most of the diabetic symptomatology of experimentally-diabetic rats, was exceptionally enticing [1]. To date, Vanadium complexes have shown considerable promise as orally available prodrugs that alleviate most of the symptoms of diabetes.
Figure 2. Checking blood glucose levels in diabetic patients
- Copper complexes in treatment of inflammation
Inflammation is the body's response to injury and infection, involving a complex biological response of the somatosensory, immune, autonomic, and vascular systems. The development of compounds with anti-inflammatory effects has been a long-term goal of researchers. Diverse copper (II) complexes have shown activity against bacteria, fungi, viruses, and yeasts or are in clinical trials while most of the reported copper (II) complexes have been examined in vitro for a variety of potential activities. According to previous reports, Anti-rheumatic drugs such as aspirin and salicylic acid derivatives have a significantly increased anti-inflammatory effect when combined with copper.
Figure 3. Diseases associated with inflammation
- Ruthenium complexes in treatment of bacterial infections
Antibiotics are substances which, even at low concentrations, inhibit the growth and reproduction of bacteria and fungi. The treatment of infectious diseases would be inconceivable without antibiotics. Today, new antimicrobial compounds are urgently needed to combat the growing threat of widespread antibiotic resistance. Among various metal complexes, ruthenium complexes are considered stable under both highly acidic and alkaline conditions. The antibacterial activity of mononuclear tris(bidentate)-ruthenium (II) complexes containing polypyridyl ligands has been reported by Dwyer and co-workers [2] decades ago. The potential effects on microbial growth inhibition of ruthenium complexes have been re-studied recently. Keene and co-workers [3] have shown that inert dinuclear polypyridylruthenium (II) complexes in which the metal centres are linked by a flexible alkane chain, exhibited excellent growth inhibition (1 to 2 μg mL-1) against a range of bacteria.
Figure 4. Bacteria
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References
- McNeill, J. H.; et al. Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science. 1985, 227: 1474-1477.
- Dwyer, F. P.; et al. Biological activity of complex ions. Nature. 1952, 170: 190-191.
- Keene, F. R.; et al. The antimicrobial activity of inert oligonuclear polypyridylruthenium (II) complexes against pathogenic bacteria, including MRSA. Dalton Trans. 2011, 40: 5032-5038.
