Transition metals anticancer

Well-characterized transition metal complexes of vitamin C (ascorbic acid) are rare, and a select number of these exhibit anticancer properties. Hollis et al. have described the first examples to be fully characterized by X-ray crystallography.316 Treatment of [Pt(H20)2L2]2+ (L = NH3, MeNH2 L2 = en, 1,2-chxn) with ascorbic acid gives either the mono- or bisascorbate species of the type cis-[PtL2(C2,Os-ascorbate)] (e.g., (125)) or m-[PtL2(C2-ascorbate)(03-ascorbate)], respectively. Interestingly, in both types of complexes, platinum(II) forms a bond with the C-2 atom of ascorbic... 

We have recently extended our interest to the analogous halfsandwich osmium-arene complexes and are exploring the chemical and biological properties of [Os(r 6-arene)(XY)Z]ra 1 complexes (Fig. 25) (105). Both the aqueous chemistry and the biological activity of osmium complexes have been little studied. Third-row transition metals are usually considered to be more inert than those of the first and second rows. Similar to the five orders of magnitude decrease in substitution rates of Pt(II) complexes compared to Pd(II), the [Os(ri6-arene)(L)X]"+ complexes were expected to display rather different kinetics than their Ru(II)-arene analogs. A few other reports on the anticancer activity of osmium-arene complexes have also appeared recently (106-108). 

In line with expectations of kinetic inertness for third-row transition metals, little interest has been vested in the development of osmium anticancer drugs, as ligand-exchange rates did not seem favorable on the timescale of cellular processes. Our work, however, shows that the kinetic lability of such complexes can be timed to such extent that anticancer activity comes within range. We have demonstrated how rational chemical design can thus be applied to osmium-arene complexes resulting in specific... 

Many organic and inorganic compounds, fibers, and particles are capable of damaging nucleic acids by generating reactive oxygen species via the reduction of dioxygen. These stimuli include different classes of organic compounds, classic prooxidants (anticancer antibiotics, various quinones, asbestos fibers, and so on), and even antioxidants, which can be oxidized in the presence of transition metal ions. 

These reactions, and in particular the ease of formation of the N(7)-0(6) chelate, may be relevant to the mechanism of action of the anticancer transition metal compounds such as m-[PtCl2(NH3)2].230... 

One of the great successes of transition metal compounds is Cisplatin. This compound, with a very simple structure (and, incidentally, not even a single carbon atom ), is one of the most successful anticancer dmgs [3]. After its serendipious discovery by B. Rosenberg, Cisplatin quickly gained clinical approval in 1978. It has inspired research efforts into literally thousands of Pt-containing compounds, from which two more have reached world-wide approval (Carboplatin and... 

Hall IH, Lackey CB, Kistlee TD, Durham RW, Jr, Russell JM and Grimes RN (2000a) Antitumor activity of mono- and dimctallic transition metal carborane complexes of Ta, Fe, Go, Mo, or W. Anticancer Res 20 2345-2354. 

As mentioned in the introduction, metallocene-type complexes based on the early transition metals were evaluated as anticancer compounds shortly after the discovery of cisplatin. While the biological activity of each of the metallocene dihalides is unique, titanocene dichloride 7 has been the subject of a number of studies and even entered clinical evaluation, although evaluation was discontinued (not due to its anti-proliferative properties), principally due to formulation problems, despite showing superior activity to certain cancers than other established drugs. This class of compound continues to be modified and studied for anticancer activity, for example, the titanocene-type derivative of tamoxifen 1, described above, and other developments described below. 

In addition to the release of carbon monoxide, transition metal carbonyl complexes have also found applications in anticancer chemotherapy [212], radiolabelling [213-216], and as photosensitisers. The cobalt complex shown in Fig. 14 a demonstrates a higher anticancer activity than cis-platin in certain mammary tiunor cells Hnes [217,218]. Complexes such as Tc-99m(I)(CO)3(OH2)3 along with hydroxymethyl phosphine derivatives [219] and the cyclopentadienyl complex shown in Fig. 14b have useful radiopharmaceutical applications, in diagnosis, using Tc, as the metal centre, and in therapy based on Re and Re isotopes [220]. 

Since the biochemical role of transition metal complexes (e.g. anticancer agents) is strongly dependent on their conformational characteristics, the structural analysis of this kind of system is of the utmost importance for the understanding of the structure-activity relationships (SAR s) underlying their antineoplastic activity. 

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