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 adenosine A(3) receptor. On the other hand, an eudistomin D derivative, BED, exhibited modest affinity to all the receptors A(1), A(2A), and A(3) but no selectivity.
Ishiyama
Haruaki
H
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Ohshita
Kengo
K
Abe
Tetsuro
T
Nakata
Hiroyasu
H
Kobayashi
Jun'ichi
J
D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D015394:Molecular Structure; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002243:Carbolines; D018047:Receptors, Purinergic P1; C520303:eudistomin D