Grancharov K C, Gorneva G A, Spassova M K, Mladenova J P
Int J Biochem. 1985;17(5):619-24. doi: 10.1016/0020-711x(85)90294-0.
The cytotoxic and cytokinetic effects, and in vitro inhibition of macromolecular synthesis by cyanopyrazoles were studied using Friend leukemia and Ehrlich ascites tumor cells. At concentrations in the range of 2.5 mM to 50 microM analog 3(5)-amino-4-cyano-5(3)-trichloromethylpyrazole (I) was highly cytotoxic and completely inhibited thymidine, uridine and leucine incorporation into macromolecular material. 24 hr incubation of FL cells with cytostatic concentrations of compound I (in the range of 2 to 0.5 microM) resulted in an accumulation of cells in the G2 + M phase. Analogs N-hydroxyethyl-3(5)-amino-4-cyano-5(3)-trichloromethylpyrazole (II) and 3(5)-amino-4-cyanopyrazole (III) were not cytotoxic at concentrations up to 5 mM and did not substantially inhibit precursor incorporation into macromolecules but exhibited a cytostatic activity. These compounds caused a decrease of FL cells in the G2 + M phase and an accumulation in the S phase. Analogs I and II displayed a similar in vivo inhibitory effect on thymidine incorporation into DNA in EAT cells. The results indicate that the cytotoxicity of cyanopyrazoles correlates with their ability to inhibit precursor incorporation into macromolecular material. On the other hand, the cytostatic action of compound I is not coupled to a block of nucleic acid synthesis.
利用Friend白血病细胞和艾氏腹水瘤细胞，研究了氰基吡唑的细胞毒性和细胞动力学效应，以及其对大分子合成的体外抑制作用。在2.5 mM至50 microM的浓度范围内，类似物3(5)-氨基-4-氰基-5(3)-三氯甲基吡唑（I）具有高度细胞毒性，能完全抑制胸苷、尿苷和亮氨酸掺入大分子物质中。用细胞抑制浓度的化合物I（2至0.5 microM）孵育FL细胞24小时，导致细胞在G2 + M期积累。类似物N-羟乙基-3(5)-氨基-4-氰基-5(3)-三氯甲基吡唑（II）和3(5)-氨基-4-氰基吡唑（III）在浓度高达5 mM时无细胞毒性，也未显著抑制前体掺入大分子，但表现出细胞抑制活性。这些化合物导致FL细胞在G2 + M期减少，并在S期积累。类似物I和II对艾氏腹水瘤细胞中胸苷掺入DNA显示出相似的体内抑制作用。结果表明，氰基吡唑的细胞毒性与其抑制前体掺入大分子物质的能力相关。另一方面，化合物I的细胞抑制作用与核酸合成的阻断无关。
