Platinum— and Palladium—Amine Complexes

The demonstrated antitumour activity of cisplatin was naturally extended to studies on antiviral effects. The complex may be used as an activator in the presence of light or oxygen to inactivate Herpes Simplex, Type 1 [21]. Further studies showed that the compound had antiviral action in vitro 

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. 

The use of complexes of cisplatin with modified nucleosides such as acyclovir has also been proposed for antiviral applications [23]. This approach is similar to that described for antitumour responses in Chapter 3. For antiviral effects, the fact that many of the antiviral nucleoside analogues are not very specific must be considered a disadvantage in this approach. Thus, although there is a distinct synergy between say, are-C, and cisplatin in antitumour effects, the therapeutic index of ara-C for a virus is almost unity and thus toxic side effects may not be overcome. The complex d5-[Pt(NH3)2(Guo)2] has also been reported to have antiviral activity [23], and also to have some antitumour activity (Section 3.5) [24]. However, the carrier approach may be more effective in antiviral therapy than in destroying tumour cells. 

Some oligonucleotides do not act by interferon induction but rather by inhibition of proviral DNA synthesis, one of the most active being single stranded poly(A) [32, 33]. In view of the demonstrated activity of the poly(A)—Rh acetate complex in tumour systems [34] and its binding specificity for adenine nucleotides [35] (Section 6.2) the effect of highly specific metal complexes on this type of interaction is of considerable interest. The synthesis of complexes specific for singly stranded DNA, especially those with little antitumour effect, should be significant. 

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