Hall I H, Izydore R A, Vital T S, Chen S Y, Miller M C, Bernal-Ramirez J A, Okwisa W A, Rajendran K G
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Anticancer Res. 1995 Jan-Feb;15(1):199-204.
The 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolinediones proved to be cytotoxic against the growth of a number of cell lines, including murine and human leukemias. HeLa suspended carcinoma, colon adencarcinoma SW480, KB nasopharynx and glioma tumors. Selected compounds were also active in the human lung bronchogenic MB-9812, and osteosarcoma TE418 screens. These derivatives were active in vivo in the Ehrlich ascites carcinoma screen in CF-1 mice at 8 mg/kg/day I.P. The mode of action in Tmol3 leukemia cells showed that the compounds reduced de novo synthesis of purines and pyrimidines and inhibited dihydrofolate reductase and ribonucleoside reductase activities. The DNA molecule was not a target although limited DNA strand scission may be possible.
1-酰基-和1,2-二酰基-4,4-二乙基-3,5-吡唑啉二酮对多种细胞系的生长具有细胞毒性，包括鼠类和人类白血病细胞系、HeLa悬浮癌细胞、结肠腺癌SW480、KB鼻咽癌和胶质瘤肿瘤细胞系。所选化合物在人肺支气管源性MB - 9812和骨肉瘤TE418筛选中也具有活性。这些衍生物在CF - 1小鼠的艾氏腹水癌筛选中，以8mg/kg/天的腹腔注射剂量在体内具有活性。在Tmol3白血病细胞中的作用模式表明，这些化合物减少了嘌呤和嘧啶的从头合成，并抑制了二氢叶酸还原酶和核糖核苷还原酶的活性。尽管可能存在有限的DNA链断裂，但DNA分子不是靶点。
