Relationship between the structure of diamine platinum(II) complexes and their cytostatic activity as measured on plant roots

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The amine substituent effect in compounds [Pt(diamine)Cl2] on inhibition of maize and cucumber root growth and branching has been investigated. The diamines used were ethylenediamine (en),N-methylethylenediamine (men),N,N-dimethylethylenediamine (N,N-dmen),N,N′-dimethylethylenediamine (N,N′-dmen),N,N,N′,N′-tetramethylethylenediamine (tmen), 1,2-propanediamine (1,2-pn), 2-methyl-1,2-propanediamine (ibn), 2,3 dimethyl-2,3-butanediamine (C-tmen), 1,3-propanediamine (1,3-pn), 2,2-dimethyl-1,3-propanediamine (C2-dm-1,3 pn),N,N-dimethyl-1,3-propanediamine (N,N-dm-1,3-pn). Increased substitution of hydrogen atoms of the amine part with CH3 groups reduces the cytostatic activity of complexes. The substitution of hydrogen atoms of NH2 and vicinal CH2 groups displays similar results. C-2 dimethylation (C-dm-1,3-pn) does not change the activity of the complex compared with (1,3-pn). It was observed that maize and cucumber roots differ in their relative sensitivity to various complexes. All complexes containing pn and their substituted analogs inhibited cucumber root growth weaker than that in maize. A comparison of obtained data with earlier published results concerning antitumor activity of complexes shows that they correlate in a similar manner with increased substitution of amino groups. Therefore, roots may be used as cheap test objects for primary screening of cytostatics. The general tendency of a decrease in cytostatic activity goes parallel with the number of Nor vicinal C-methyl groups and seems to arise from a decrease in hydrogen-bonding potential; however, some other possible reasons are also discussed. The activity discrimination by different species in our experiments and clearly different results forN,N-dimethylation depending on the chelate ring size (en and pn derivatives) on maize cannot be attributed to slower ligand-exchange kinetics from methylation. It is possible to assume that the major role in cytostatic activity of platinum complexes belongs to a cell repair system, i.e. the ability to eliminate platinum diamine fragments from DNA, depending on the number and strength of hydrogen bonds formed by thecis-diamine fragment.