Polyamines, platinum

Platinum polyamines can be readily synthesized with good control on th chain length through reaction of salts of PtX with diamines. The... 

This paper presents preliminary biological assay results related to potential antineoplastic activity for select platinum polyamines of Form IV. 

Figure 2. Structures of platinum polyamines utilized in the biological testing.

The data given In Tables 5 and 6 are offered to Illustrate the variety of results. Thus for Poliovirus, platinum polyamines can effect an Increase or decrease In the growth of the virus or exhibit no effect at concentrations below that where the HeLa cells are affected. Similar results are found for the polyamines In L929 cells Infected with EMC strain MM. Thus with treatment for 24 hours, polymers 9,11 and 12 suppressed viral replication (Table 6). With the exception of polymer 6, all of the polymers suppressed EMC viral replication when treatment was extended to 48 hours. Again viral replication was affected at polyamlne concentrations well below that necessary to Inhibit the L929 cells. 

Table 4 Cytotoxicity and antitumor activity of platinum polyamine complexes in murine leukemia sensitive (L1210) and resistant to CDDP (L1210/CDDP) and in the LX-1 human tumor xenografP...

Polymers should be eliminated more slowly, reducing the exposure of the kidneys, increasing the concentration of the compound that is retained by the body, and permitting lower effective doses of the drug to be used. Second, platinum polyamines should show... 

Which of these four potential advantages, if any, actually occurs with the platinum polymers is currently being studied. Approximately two dozen platinum polyamines have been synthesized, and some show biological activity while others do not (126-128). Several of the polymers properties are being explored and correlated with polymer activity in an effort to discover why certain polymers are active while others are inactive. Such factors as the nature of the diamine component, the extent to which a polymer is transported into the cell, the rate of aquation, etc., could all influence the biological activity of a polymer. Two other properties that could control polymer activity are the size of a polymer and the tendency of a polymer to degrade, and these will be the subject of discussion here. 

Platinum polyamines can be synthesized using a wide variety of diamines, including pyridine derivatives, pyrimidines, amino acids, and more complicated compounds such as methotrexate. 

The biological activity of the platinum polyamines was tested in cell culture using two cell lines derived from mouse fibroblasts. Balb/3T3 cells resemble normal cells in their growth properties m-MSV Balb/3T3 cells have been transformed and resemble cancer cells in their growth properties. 

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... 

In general, agents capable of inhibiting one RNA virus will inhibit other RNA viruses but each DNA virus must be evaluated separately. The platinum polyamines were studied against RNA viruses. The behavior toward RNA viruses was varied with some showing little activity but the majority showing inhibition of viral replication at polymer concentrations below which tumoral inhibition is found (< 1 (tg/ml). 

The effect of platinum polyamines on the transformation of 3T3 cells by SV40 virus was also studied [111]. In summary, these polymers showed no effect on the transformation process. 

A further consideration involves the absence or presence of bridging carbonyls which would result in the platinum existing in in octahedral geometry. This possibility does not exist for the synthesis of platinum polyamines where the platinum complex exists as a square planar structure. 

Thus while the platinum II polyureas and polythioureas exhibit some tumoral inhibition they are less active than analogous platinum polyamines. 

The synthesis of palladium polyamines (2) is a straightforward extension of our previous work involving the synthesis of the analogous platinum polyamines ( 6,7). The geometrical structure of the units about the palladium atom is believed to be as depicted in 2 where the like units are cis to one another. This is supported by the trans effect (8) discussed in the previous paper and by spectroscopic measurements cited in the following paragraphs. 

Product yield and molecular weight results are given in Table 4. Compared to the analogous platinum polyamines, reaction is somewhat slower. Good (80J plus) yields of the platinum polyamines typically occur (for chlorides) within 48 hours. 

A second difference is the poorer, more limited solubility of the palladium compounds compared to the analogous platinum polyamines. Most of the platinum polyamines thus far synthesized are soluble in a number of dipolar aprotic solvents with some even soluble in chloroform. Only the palladium polyamines derived from dissymmetrical diamines exhibit solubility in any attempted solvent and here solubility is limited to only dipolar aprotic solvents to an extent of 3% and less. Solubilization in dipolar aprotic liquids is dependent on a number of factors - the major one being the ability of the dipolar aprotic liquid molecules to polarize the solute molecules. The smaller size and corresponding poorer polarizability of the palladium atom is probably responsible for this trend. A further, but related factor, is the possible greater tendency for the palladium polymers to form crystalline regions. 

Effect of Tetramisole and Its Platinum Polyamine on Mice Infected With Encephalomyocarditis-Variant-D Virus 223... 

There are two main aspects of study for the degradation of the platinum polyamines. First, the rate of degradation is important since this should be indicative of the mobility, location, and half life of the polymer in the body. Monomeric platinum compounds typically have more mobility, are less limited to location, and have shorter half lives (less than 24 hours) than their polymeric counterparts. Second, determining the... 

Tetramisole and its platinum polyamine were examined for their effects on EKC-D virus-induced diabetes in outbred ICR Swiss male mice. Both tetramisole and its isomer levamisole are potent immunomodulators capable of restoring immune responsiveness to normal levels in certain immune deficient patients while exerting no demonstrable effect on normal individuals The immunomodulatory effects of levamisole have been more... 

---