Sood A, Spielvogel B F, Shaw B R, Carlton L D, Burnham B S, Hall E S, Hall I H
Boron Biologicals, Inc., Raleigh, North Carolina 27606.
Anticancer Res. 1992 Mar-Apr;12(2):335-43.
The guanine, inosine, adenine and cytidine deoxyriboside cyanoboranes proved to be cytotoxic and possess in vivo antineoplastic activity against murine and human single cells and cultured cells derived from solid tumor lines. The agents preferentially inhibited DNA synthesis in Tmolt3 leukemic cells. The enzyme sites of drug inhibition of two active derivatives were DNA polymerase-alpha and de novo purine synthesis at the regulatory sites, PRPP amido transferase and IMP dehydrogenase. Moderate inhibition by the agents of TDP kinase and ribonucleoside reductase activities also occurred. Kinetic studies showed that IMP dehydrogenase activity was inhibited the earliest of all of the enzymes affected by the drugs. The d(ATP) pools were also reduced by drug treatment. DNA strand scission was evident after 24 hr incubation at 100 microM of drug. The 14C-cytidine-cyanoborane drug was rapidly taken up over 6 hr and most effective uptake was shown by rapidly dividing cells. The drug was bound to DNA, RNA and protein in Tmolt3 leukemic cells.
鸟嘌呤、肌苷、腺嘌呤和胞苷脱氧核糖苷氰基硼烷被证明具有细胞毒性，对源自实体瘤系的小鼠和人类单细胞及培养细胞具有体内抗肿瘤活性。这些药物优先抑制Tmolt3白血病细胞中的DNA合成。两种活性衍生物的药物抑制酶位点是DNA聚合酶-α以及在调节位点的从头嘌呤合成、磷酸核糖焦磷酸酰胺转移酶和肌苷酸脱氢酶。这些药物对胸苷二磷酸激酶和核糖核苷还原酶活性也有适度抑制作用。动力学研究表明，肌苷酸脱氢酶活性是受这些药物影响的所有酶中最早受到抑制的。药物处理后d(ATP)池也减少。在100微摩尔药物浓度下孵育24小时后，DNA链断裂明显。14C-胞苷-氰基硼烷药物在6小时内迅速被摄取，快速分裂的细胞显示出最有效的摄取。该药物与Tmolt3白血病细胞中的DNA、RNA和蛋白质结合。
