Halogenated pyrrolopyrimidine analogues of adenosine from marine organisms: pharmacological activities and potent inhibition of adenosine kinase.
Two novel halogenated pyrrolopyrimidine analogues of adenosine, isolated from marine sources, have been examined for pharmacological and biochemical activities. 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine, from a sponge of the genus Echinodictyum, had bronchodilator activity at least as potent as theophylline but with a different biochemical profile; unlike theophylline it had no antagonist activity at CNS adenosine receptors and it was quite a potent inhibitor of adenosine uptake and adenosine kinase in brain tissue. 5'-Deoxy-5-iodotubercidin, isolated from the red alga Hypnea valentiae, caused potent muscle relaxation and hypothermia when injected into mice. This compound was a very potent inhibitor of adenosine uptake into rat and guinea-pig brain slices and an extremely potent inhibitor of adenosine kinase from guinea-pig brain and rat brain and liver. Neither of these two pyrrolopyrimidine analogues was a substrate for, or an inhibitor of, adenosine deaminase. Neither compound appeared to have any direct agonist activity on guinea-pig brain adenosine-stimulated adenylate cyclase (A2 adenosine receptors). 5'-Deoxy-5-iodotubercidin is unique in two respects: it appears to be the first naturally-occurring example of a 5'-deoxyribosyl nucleoside and is the first example of a specifically iodinated nucleoside from natural sources. It may be the most potent adenosine kinase inhibitor yet described and, by virtue of its structure, may prove to be the most specific.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D001921:Brain / Q000378:metabolism; D001993:Bronchodilator Agents / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008386:Marine Biology; D051379:Mice; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D051381:Rats; D012263:Ribonucleosides / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology*
C040540:4-amino-5-bromopyrrolo(2,3-d)pyrimidine; C040541:5'-deoxy-5-iodotubercidin; D001993:Bronchodilator Agents; D012263:Ribonucleosides; D013806:Theophylline; D010770:Phosphotransferases; D000248:Adenosine Kinase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D000225:Adenine; D000241:Adenosine; D014372:Tubercidin