Abstract
The antitumour activity of four N-6-substituted PMEDAP derivatives, Me2NEt-PMEDAP, allyl-PMEDAP, Me-2-PMEDAP and cypr-PMEDAP, selected on the basis of their in vitro cytostatic activity, was studied in an in vivo model of haematological malignancy of inbred Sprague-Dawley rats. These compounds are believed to serve as the prodrugs of another (phosphonomethoxy) ethyl derivative, PMEG (9-[2-phosphonomethoxy) ethyl] guanine.
We compared their toxicity and ability to inhibit tumour development in two different dosage regimes with those of their parent compound PMEDAP, as well with PMEG. The study confirmed the anticancer efficacy of the parental compound PMEDAP.
Unlike PMEDAP, its N-6-mono- and disubstituted congeners Me2NEt-PMEDAP, allyl-PMEDAP and Me-2-PMEDAP were less potent or exhibited the same antineoplastic effect as PMEDAP. cypr-PMEDAP significantly decreased the survival of lymphoma-bearing rats due to high toxicity, which was approximately the same as that of PMEG, Therefore, these acyclic nucleoside phosphonates substituted at the 6-position of 2,6-diaminopurine ring do not seem to be promising drugs for the treatment of haematological malignancies.