Metal complexes antiviral activity

Although there has heen a great deal of research concerning how platinum(II) complexes hind to biological molecules and the hkely mechanism of antitumor activity of these platinum-containing species, far less attention has heen paid to the properties of other metal complexes in this arena. Recent attention has fallen on cohalt(II)-Schiff hase complexes, as several have heen discovered to have promise as antiviral agents. A review of recent work has appeared elsewhere [64], so the topic will not he covered here however, in addition to focusing on recent developments, emphasis is placed on the introduction of the new head unit, 3,6-diformylpyridazine (13), into Schiff-hase macrocyclic electrochemistry. 

Some antioxidants possess antimicrobial properties, such as propyl gallate and butylated hydroxy anisole, which are somewhat effective against bacteria. Butylated hydroxy toluene has demonstrated some antiviral activity. Compatibility of antioxidants with the drug, packaging system and the body should be studied carefully. For example, tocopherols may be absorbed onto plastics ascorbic acid is incompatible with alkalis, heavy metals, and oxidizing materials such as phenylephrine, and sodium nitrite and propyl gallate forms complexes with metal ions such as sodium, potassium and iron. 

Metal ion complexes of antivirally active acyclic nucleoside phosphonates as nucleotide analogs 04CSR191. 

The ubiquitous chelates of 1,10-phenanthroline were studied some time ago for their antiviral activity [17]. The inhibitory effect of various chelates on the multiplication of influenza virus (Melbourne strain) in chick chorioallantoic membrane in vitro was studied, and the most effective complex was shown to be the [Ru(acac) (3,5,6,8-Me4-l,10-phen)2] cation, which inhibited multiplication at concentrations of 6 X 10 M(—log M = 6.2). Other chelate complexes were active at concentrations of 10 to 10 M. A structure—activity study of metal chelates showed, however, that for a given chelate ligand, more labile complexes such as those of Cd or Cu were more active than their inert counterparts, the order for doubly-charged (2+) chelates being Cd(II) > Cu(II) > Zn(II) > Mn(II) > Fe(II) > Co(II) > Ni(II) > Ru(II) [18]. This correlation coincided with that found for some antibacterial effects (Chapter 9). Further studies showed that the virostatic activity may be manifested by either direct inactivation of the virus (possibly through dissociation of the more labile chelates) or by direct action on the host cell (for inert complexes). The latter effect is indicated by the fact that the trend in virostatic activity is similar to that in antitumour activity [19] (see also Chapter 6) and the fact that, of the various 1,10-phenanthrolines studied, the tetramethyl derivatives most easily penetrate cells [20]. 

Chelating agents may manifest their antiviral activity by metal sequestration and, as with bacteria and parasites, the natural differences between the host and invading cells may be exploited. Chelating agents with antiviral activity include the thiosemicarbazones, 1,10-phenanthrolines and phosphonoacetates. The latter compounds may act by zinc chelation. Metal complexes with antiviral action are platinum and palladium amines, as well as the antibacterial silver and mercury species. 

In vitro, cydopentadienyl metal complexes were able to suppress the proliferation of normal or transformed tumor cells. Best activity was found for vanadocene dichloride in this respect. In vivo, numerous of the cydopentadienyl metal complexes inhibited the development of diverse experimental animal tumors (e.g., Ehrlich asdtes tumor, sarcoma 180, B16 melanoma, colon 38 cardnoma and Lewis lung cardnoma) and the growth of human cardnomas xenografted to nude mice. Espedally certain titanocene and ferricenium compoimds were cytostatically effective against human colorectal cardnomas. Moreover, titanocene complexes were shown to be antiviral agents and potent antiinflammatory compounds comparable to phenylbutazone. 

Certain optically active octahedral transition metal cations exhibit very effective antiviral or antibacterial activity. As described in the present book, platinum(II) complexes are used as effective antitumor agents. New discoveries should be expected in this field. 

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