Specificity of adenosine deaminase inhibitors

The specificity of the potent adenosine deaminase inhibitors deoxycoformycin (covidarabine), coformycin and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), has been assessed in Ehrlich ascites tumor cells in vitro and in cultured mouse lymphoma L5178Y cells. EHNA is both less potent an inhibitor of adenosine deaminase than deoxycoformycin, and is less specific. High concentrations of deoxycoformycin and EHNA inhibit all pathways of purine ribonucleotide synthesis, and inhibit the conversion of inosinate to adenine and guanine nucleotides. These drugs also inhibit purified adenylate deaminase, but inhibition of this enzyme in intact cells can only be detected at high rates of deamination of adenylate. Deoxycoformycin potentiates the toxicity of adenine against cultured cells.