Biological activities of 3-isoadenosine

Abstract An isomer of adenosine, 3-β- d -ribofuranosyladenine (3-isoadenosine), has been studied in a number of bacterial and mammalian cell systems. While 3-isoadenosine readily supported the growth of the adenine-requiring Escherichia coli B97, it failed to support the growth in tissue culture of a murine cell line rendered dependent on an exogenous purine source by the folic acid antagonist amethopterin. 3-Isoadenosine inhibited the growth of various mammalian cell lines in Eagle's medium at levels of 10 −4 to 10 −6 M and it displayed a cytotoxicity for the lymphoblastic leukemia cell line L5178Y of the same order as that of 6-azauridine. When tested by an agar overlay method, 3-isoadenosine also inhibited the growth of Adeno III virus in tissue culture. In order to investigate the inhibitory activity of 3-isoadenosine, comparative experiments were carried out in the above systems with other nucleoside analogs (psicofuranine, pseudouridine, triacanthine, etc.), and an unsuccessful attempt was made to reverse this inhibition with nucleosides and other complex materials. A daily dose of 3 mg/kg given intraperitoneally to mice for ten days was well tolerated but 6.0 mg/kg was toxic. The final phase of this study was the evaluation of 3-isoadenosine in tumor-bearing and virus-infected animals. The interpretation of the observed biological activity in terms of the underlying biochemical mechanisms has been attempted by comparison of the activities of 3-isoadenosine and of related nucleosides and other agents. This comparison revealed a striking similarity in the characteristics of inhibition of mammalian cells in tissue culture by 3-isoadenosine and by 7-deaza-adenosine.