Rhodium complexes antitumour activity

A comparison of platinum group metal complexes is illustrative of the relatively narrow window of reactivity and stability which generates complexes with suitable antitumour activity. Table 6.1 collects some comparative data of structurally analogous complexes, containing only ammonia and chloride ligands. The palladium complex, like the octahedral iridium analogue, shows little activity, while those of rhodium and ruthenium are somewhat intermediate. Palladium complexes are more labile than those of platinum, reacting approximately 10 times faster, and it is reasonable to accept that the palladium complex will be too reactive in vivo for any... 

The complex m r-[RhCl3(NH3)3j has been reported to have good activity, the best of the rhodium—amine complexes, but it is very insoluble [2]. Rhodium complexes are of interest because of the demonstration of their antibacterial action [7] (see Chapter 9) in structures of type [RhCl2(py)4] , which show, however, only marginal antitumour activity. Conversely, the most antitumour active rhodium species in general show few antibacterial... 

An interesting series of complexes with antitumour activity is that of the rhodium carboxylates, whose structure is a dimer containing bridging carboxylates ... 

The biological studies on the rhodium carboxylates have been reviewed and discussed [3, 9, 10]. A number of interesting points have emerged, emphasizing the diversity of metal-based complexes with antitumour activity, although for rhodium carboxylates the acute toxicity probably eliminates these complexes from further development. The results are summarized below ... 

Non-platinum metal complexes with antitumour activity in murine screens are known for a wide diversity of structural types and the transition metals most studied include rhodium, ruthenium, gold, copper and titanium. The spectrum of activity is generally different to cisplatin (Ti, Au) and in some cases the complexes show lack of cross-resistance with cisplatin-resistant lines. 

An interesting aspect of these complexes is the relative activity of the free complexes and their berenil analogues in tumours and trypanosomes. Thus, while rhodium butyrate is very active in vitro in LI 210 emd not active vs. T. rhodesiense, the opposite is true for its bridged berenil analogue, [Rh2(OBu)3(Ber)J (Ber = anion of berenil), which has only slight antitumour activity. Thus, a situation is emerging where the relative activities of two closely related species are dictated by the activity of the carrier group. 

Complexes with some antitumour but not trypanocidal activity were cw-[RuCl2(DMSO)4] and rhodium acetate. Of the relatively small number of complexes studied, the observation of activity in two series indicates that the antitumour/trypanocide analogy holds for metal complexes. In this respect, it is of interest to note that mAZ5-[PtCl2(NH3)2] is inhibitory in vitro to T. brucei gambiense at doses 10 times higher than the cw-isomer (40 vs 4 //M, respectively) [71]. 

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