Enhancement of the biological activity of adenosine analogs by the adenosine deaminase inhibitor 2'-deoxycoformycin

Abstract

The potent adenosine deaminase inhibitor 2'-deoxycoformycin ((R)-3-(2-deoxy-beta-D-erythropentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol) inhibits the enzymic inactivation and potentiates the cytotoxic activity of a variety of adenosine analogs in the P388 murine leukemia cell culture system. The activity of all seven adenosine analogs examined was enhanced by 2'-deoxycoformycin with the exception of tubercidin (7-deaza-adenosine) which is not a substrate for the deaminase. In vivo, 2'-deoxy-coformycin potentiated the antineoplastic activity of 9-beta-D-xylofuranosyladenine in mice with P388 murine leukemia.