Platinum antiviral activity

A number of platinum polyamines were tested for antiviral activity in tumor cells [111]. For instance, the polymer from tetrachloroplatinate and 2,6-diamino-3-nitroso-pyridine (Scheme 8.34) which exhibited a cell differential ratio of 3.4, was tested at a concentration of 2.2 Xg/ml on L929 cells infected with... 

A were effective against herpes simplex virus-1 (HSV-land 11) [82, 83]. Eudistomin K sulfoxide and eudistomin K have high activities against polio vaccine type-1 virus. Platinum (If) and palladium (11) complexes of harmaline, harmalol, harmine, and harman and ( )-Debromoeudistomin K were also observed to exhibit antiviral activities against influenza virus (A and B) and herpes virus [84]. Recently, harman and its derivatives were found to possess anti-HIV activities against human peripheral blood mmuHiuclear (PBM) cells [85]. 

In this context the use of DMSO as carrier has been claimed to be applicable [23]. The clinically used pyrimidine analogue, iodouridine, is only sparingly water-soluble and is used in a DMSO solution for topical application. The reactivity of platinum complexes in DMSO, however, could be a potential problem and the approaches outlined in Section 3.3 may well be applicable for a pharmaceutically suitable formulation of antiviral activity. The toxic side effects of the platinum complexes, if also manifested in a localized application, would be a serious drawback in this present context since the desired selectivity is not present. Again, it is probable that the antiviral effect is manifested by killing of the host cell. 

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. 

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. 

The new examples reported include the preparation of antiviral, antibacterial, and antitumor agents by coupling sugar isothiocyanates and such biologically active amines as triazole derivatives,195 mitomycin,196 isothia-zolopyrimidines,40 and also platinum compounds.197 Other A -nuclcophiles such as hydrazine,37 isothiourea,198 and guanidine derivatives199 have been similarly coupled to sugar isothiocyanates. 

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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