Apoptotic effects of imidazo[1,2-a]pyrazine derivatives in the human Dami cell line.

ABSTRACT

cAMP-elevating agents like phosphodiesterase inhibitors and purines have 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), PAB15 (6-bromo-8-(ethylamino)imidazo[1,2-a]pyrazine), PAB23 (3-bromo-8-(methylamino)imidazo[1,2-a]pyrazine) on the growth of the Dami cell line in comparison to that of adenosine. The growth effect of PAB13, PAB15 and PAB23 was investigated in relation to their phosphodiesterase-inhibitory 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, respectively and 100% for adenosine. Cell viability was affected in a concentration-dependent manner by PAB13, PAB15 and adenosine, with a correlation between growth inhibition and cytotoxicity. These effects of imidazo[1,2-a]pyrazine derivatives were found to be unrelated to an action on purinoceptors, but rather appear quantitatively linked to their ability in inducing apoptosis through their cAMP-increasing and phosphodiesterase-inhibitory potency.