Synthesis of eudistomin D analogues and its effects on adenosine receptors

Six analogues (1–6) of eudistomin D, a β-carboline alkaloid from a marine tunicate Eudistoma olivaceum, were synthesized, and their affinity and selectivity for adenosine receptors A1, A2A, and A3 were examined. All the synthetic compounds 1–6 did not show affinity to the adenosine A1 receptor. δ-Carboline 3 exhibited the most potent affinity to the adenosine receptor A3 among compounds 1–6. δ-Carbolines 3 and 4 showed better affinity than the corresponding β-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 A3 receptor. On the other hand, an eudistomin D derivative, BED, exhibited modest affinity to all the receptors A1, A2A, and A3 but no selectivity.

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