Synthesis of eudistomin D analogues and its effects on adenosine receptors

Six analogues (1-6) of eudistomin D, a beta-carboline alkaloid from a marine tunicate Eudistoma olivaceum, were synthesized, and their affinity and selectivity for adenosine receptors A(1), A(2A), and A(3) were examined. All the synthetic compounds 1-6 did not show affinity to the adenosine A(1) receptor. delta-Carboline 3 exhibited the most potent affinity to the adenosine receptor A(3) among compounds 1-6. delta-Carbolines 3 and 4 showed better affinity than the corresponding beta-carbolines 1 and 2, respectively, while N-methylation (2, 4, and 6, respectively) of the pyrrole ring in 1, 3, and 5 resulted in the reduced affinity to the adenosin A(3) receptor. On the other hand, an eudistomin D derivative, BED, exhibited modest a. nity to all the receptors A(1), A(2A), and A(3) but no selectivity. (C) 2008 Elsevier Ltd. All rights reserved.