The novel acyclic
nucleoside phosphonate analogue 9-(2-phosphonylmethoxyethyl)-N6-cyclopropyl-2,6-diaminopurine (
cPr-PMEDAP) was shown in vitro to act as an intracellular
prodrug of 9-(2-phosphonylmethoxyethyl)guanine (
PMEG). We compared the in vivo antitumor efficacy and selectivity of
cPr-PMEDAP, its progenitor
PMEDAP, and
PMEG in a rat
choriocarcinoma tumor model. The rats, inoculated with rat
choriocarcinoma (RCHO) cells under the renal
capsule, were treated IP during 10 days. Macroscopical and histological examination of the RCHO-inoculated kidneys was performed at two time points (i.e., immediately after the end of treatment or after an additional
drug-free period of 2 weeks). Complete inhibition of
choriocarcinoma tumor development was achieved upon treatment with
cPr-PMEDAP,
PMEG, and
PMEDAP at a daily dose of 10, 1, and 50 mg/kg, respectively. At these doses, all three compounds produced moderate to strong toxicity (evidenced by
atrophy of lymphoid organs and reduced
body weight gain). When compared at the maximum tolerated (sublethal) doses (i.e., 0.5, 10, and 50 mg/kg for
PMEG,
cPr-PMEDAP, and
PMEDAP, respectively),
cPr-PMEDAP proved superior to
PMEG and
PMEDAP in achieving a complete inhibition of
tumor development. Also, whereas
PMEG was unable to produce a prolonged antitumor effect, the animals treated with
cPr-PMEDAP still showed prominent inhibition of
tumor development when
tumor size was evaluated at 2 weeks after end of treatment. Based on its efficacy and therapeutic safety,
cPr-PMEDAP can be regarded as a promising
antitumor agent, which merits further in vivo evaluation in additional
tumor models for human
neoplasms.