Hall I H, Elkins A, Sood A, Tomasz J, SpielVogel B F
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Anticancer Res. 1996 Nov-Dec;16(6B):3709-14.
Base substituted boronated nucleosides and phosphate modified nucleotides were examined for their cytotoxic activity in both murine and human tissue cultured cancer cells. These derivatives demonstrated better activity against the growth of single cell suspensions than solid cell tumor cell growth. A detailed mode of action study showed that 2'deoxyriboadenosine-N7-cyanoborane 6 suppressed Tmolt3 DNA synthesis preferentially with the major target of the agent being the purine de novo pathway. The activities of one of the regulatory enzymes of the pathway were reduced by the agents, i.e. PRPP-amido transferase. Other sites in the cell which were moderately affected by the agent were nucleoside kinase activities. DNA polymerase alpha and dihydrofolate reductase activities. The DNA molecule itself did not appear to be a target of the compound.
对碱基取代的硼化核苷和磷酸修饰的核苷酸在小鼠和人组织培养癌细胞中的细胞毒性活性进行了研究。这些衍生物对单细胞悬液生长的活性比对实体肿瘤细胞生长的活性更好。一项详细的作用机制研究表明，2'-脱氧核糖腺苷-N7-氰基硼烷6优先抑制Tmolt3 DNA合成，该药物的主要作用靶点是嘌呤从头合成途径。该途径的一种调节酶的活性被这些药物降低，即磷酸核糖焦磷酸酰胺转移酶。细胞中受该药物中度影响的其他位点是核苷激酶活性、DNA聚合酶α和二氢叶酸还原酶活性。DNA分子本身似乎不是该化合物的作用靶点。
