[The effect of chemically modified polyamine analogs on polyamine and putrescine biosynthesis in a cell-free test...

Nine novel chemically modified polyamine analogues were synthesized as potential antitumor agents and evaluated for their capacity to inhibit biosynthesis of polyamines in cell-free system of rat hepatoma G-27. All analogues (numbers I-IX) were used in a final concentration of 10(-4) M. Compounds I-VI modified by adenosine demonstrated activation both ODC activity (except substance I) and polyamine synthesis. The degree of activation depended on the length and quantity of methylene groups in the structure of the analogues. Compound I inhibited ODC activity stronger than its known inhibitor DFMO. On the other hand, substances VII-IX modified by two uracils significantly reduced polyamine levels as well as inhibited the ODC activity more effectively than DFMO. These results indicate that in cell-free system of rat hepatoma G-27 new analogues I and VII-IX are cap able of to some extent inhibiting biosynthesis of polyamines. These drugs might also be useful both as experimental approaches for investigation of peculiarities of polyamine metabolism, and possible application of these substances as antineoplastic agents.