V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.
Bull Exp Biol Med. 2020 Jun;169(2):262-265. doi: 10.1007/s10517-020-04864-z. Epub 2020 Jul 10.
The effects of 5-hydroxypyrimidine derivatives SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine chlorohydrate) on the tumor growth and survival of male C57BL/6 mice with transplanted Lewis lung epidermoid carcinoma (LLC) were studied in animals receiving intraperitoneal treatment on days 2-15 of tumor development. Compound SNK-578 in a dose of 10 mg/kg significantly inhibited tumor growth (by 3.6 times; 72.2%) in 7 days after the treatment was discontinued, while compound SNK-411 in a dose of 25 mg/kg only negligibly reduced tumor volume (by 41.7%). A combination of course of SNK-411 (25 mg/kg) and single intraperitoneal dose of doxorubicin (4 mg/kg) significantly inhibited the tumor growth (by 2.2 times; 55.2%), while the combination of SNK-578 (10 mg/kg) with doxorubicin (4 mg/kg) was in fact ineffective. The median survival of animals with untreated LLC was 28 days. Median survival of mice injected with SNK-578 (10 mg/kg) was 43 days, hence, the lifespan of mice with LLC was by 38.6% longer after the treatment. Two of ten mice in this group developed no tumors.
研究了 5-羟嘧啶衍生物 SNK-411（2-异丁基-4,6-二甲基-5-羟嘧啶）和 SNK-578（2-异丁基-4,6-二甲基-5-羟嘧啶盐酸盐）对荷瘤 C57BL/6 雄性小鼠移植的 Lewis 肺表皮样癌细胞（LLC）肿瘤生长和存活的影响。在肿瘤发展的第 2-15 天接受腹腔内治疗的动物中，研究了化合物 SNK-578（10mg/kg）剂量显著抑制肿瘤生长（7 天后抑制率为 3.6 倍，为 72.2%），而化合物 SNK-411（25mg/kg）剂量仅轻微减少肿瘤体积（减少 41.7%）。SNK-411（25mg/kg）疗程和单次腹腔内阿霉素（4mg/kg）剂量的联合显著抑制肿瘤生长（抑制率为 2.2 倍，为 55.2%），而 SNK-578（10mg/kg）与阿霉素（4mg/kg）的联合实际上无效。未经处理的 LLC 动物的中位存活期为 28 天。注射 SNK-578（10mg/kg）的小鼠的中位存活期为 43 天，因此 LLC 小鼠的寿命在治疗后延长了 38.6%。该组中有 2 只 10 只小鼠未发生肿瘤。
