APOPTOTIC EFFECTS OF IMIDAZO[1,2-A]PYRAZINE DERIVATIVES IN THE HUMAN DAMI CELL-LINE

cAMP-elevating agents like phosphodiesterase inhibitors and purines ha ve been shown to induce apoptosis. In the present work we have studied the effects of imidazo[1,2-a]pyrazine derivatives with a purine-like structure: PAB13 (6-bromo-8-(methylamino)imidazo[1,2-a]pyrazine), PAB1 5 (6-bromo-8-(ethylamino)imidazo[1,2-a]pyrazine), PAB23 (3-bromo-8-(me thylamino)imidazo[1,2-a]pyrazine) on the growth of the Dami cell line in comparison to that of adenosine. The growth effect of PAB 13, PAB15 and PAB23 was investigated in relation to their phosphodiesterase inh ibitory action and their activity on purinoceptors. Inhibition in cell growth was up to 71.0%, 76.3% and 89.7% for PAB23, PAB13 and PAB15, r espectively and 100% for adenosine. Cell viability was affected in a c oncentration-dependent manner by PAB13, PAB15 and adenosine, with a co rrelation between growth inhibition and cytotoxicity. These effects of imidazo[1,2-a]pyrazine derivatives were found to be unrelated to an a ction on purinoceptors, but rather appear quantitatively linked to the ir ability in inducing apoptosis through their cAMP-increasing and pho sphodiesterase-inhibitory potency.