Effect of 2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine on the Growth of Lewis Lung Carcinoma and Survival of Mice

Abstract

Experiments on male C57Bl/6 mice with transplantable Lewis lung epidermoid carcinoma were performed to evaluate the effect of early or delayed administration of compound SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) on tumor growth and animal survival. Intraperitoneal injection of SNK-411 in doses of 25 and 50 mg/kg on days 2-8 of tumor growth was followed by significant inhibition of tumor growth (by 1.8 and 2.2 times, respectively, in comparison with the untreated control). Administration of this compound on days 8-15 of tumor development had little effect on tumor growth. SNK-411 in doses of 25 and 50 mg/kg (both dosing regimens) significantly increased survival rate and lifespan of animals with tumors. The drugs for verification of this model (Fluorofur, 400 mg/kg; and doxorubicin hydrochloride, 4 mg/kg) were injected intraperitoneally on days 2-4 and 8-10 of tumor development. Administration of Fluorofur and doxorubicin hydrochloride at the late stage was accompanied by significant inhibition of tumor growth (by 1.6 and 1.4 times, respectively). The increase in the survival rate of animals receiving the cytostatic according to standard dosing regimens was less significant than in experiments with SNK-411.

Correction of serum prooncogenic cytokines and metastases by 5-hydroxypyrimidine derivatives and doxorubicin after removal of a primary tumor node in mice with the Lewis lung epidermoid carcinoma

“…A single intravenous injection of doxorubicin (4 mg/kg) on day 14 of tumor development, as well as its combination with oral administration of SNK-411 (25 mg/kg), insignificantly changed in the average number of metastases in these groups (Table 1). This differs from previously obtained data on doxorubicin administration on day 2 of the development of LLC and B-16 melanoma and increased the antimetastatic action when it was co-administered intravenously with SNK-411 and SNK-578 [5,6].…”

“…During subcutaneous inoculation of LLC and B-16 melanoma tumor cells (5×10 6 ) inducing formation of a primary tumor node in C57BL/6 mice, SNK-411 and SNK-578 showed antitumor and antimetastatic activity [5]. In the LLC model, on day 21 after tumor inoculation, MII in the lungs was 61.4% after 14 days of intraperitoneal (i.p.)…”

“…In the LLC model, on day 21 after tumor inoculation, MII in the lungs was 61.4% after 14 days of intraperitoneal (i.p.) administration of 50 mg/kg SNK-411 from day 2 to day 15 of the tumor development [5]. In the B-16 melanoma model, monotherapy with SNK-578 for 14 days…”