Antitumor characteristics of the conjugate of N4-(4-carboxybutyryl)-ara-C with ethylenediamine-introduced dextran and its resistance to cytidine deaminase.
{"title":"Antitumor characteristics of the conjugate of N4-(4-carboxybutyryl)-ara-C with ethylenediamine-introduced dextran and its resistance to cytidine deaminase.","authors":"H Onishi, P Pithayanukul, T Nagai","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>By oxidation of dextran, and reduction of the Schiff bases formed by reaction of the oxidised dextran with diaminoalkanes, several diaminoalkane-introduced dextrans were prepared and evaluated as drug carriers. Conjugates between N4-(4-carboxyburyryl)-1-beta-D-arabinofuranosylcytosine (glu-ara-C) and such drug carriers were prepared, and selected conjugates were tested in vivo, and investigated for inhibitory effects on cytidine deaminase. Ethylenediamine-introduced dextran prepared under 10% oxidation conditions was found to be most useful as a drug carrier from its chemical characteristics and toxicity evaluation in BDF1 mice. The conjugate obtained from glu-ara-C and ethylenediamine-introduced dextran 2000 showed high antitumor activity, significant at the relatively low dose of 100 mg equivalent ara-C/kg, in BDF1 mice bearing L1210 leukemia cells. Glu-ara-C and the conjugate were unaffected by cytidine deaminase under conditions in which 1-beta-D-arabinofuranosylcytosine was degraded rapidly to 1-beta-D-arabinofuranosyluracil.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"6 4","pages":"273-80"},"PeriodicalIF":0.0000,"publicationDate":"1990-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug design and delivery","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
By oxidation of dextran, and reduction of the Schiff bases formed by reaction of the oxidised dextran with diaminoalkanes, several diaminoalkane-introduced dextrans were prepared and evaluated as drug carriers. Conjugates between N4-(4-carboxyburyryl)-1-beta-D-arabinofuranosylcytosine (glu-ara-C) and such drug carriers were prepared, and selected conjugates were tested in vivo, and investigated for inhibitory effects on cytidine deaminase. Ethylenediamine-introduced dextran prepared under 10% oxidation conditions was found to be most useful as a drug carrier from its chemical characteristics and toxicity evaluation in BDF1 mice. The conjugate obtained from glu-ara-C and ethylenediamine-introduced dextran 2000 showed high antitumor activity, significant at the relatively low dose of 100 mg equivalent ara-C/kg, in BDF1 mice bearing L1210 leukemia cells. Glu-ara-C and the conjugate were unaffected by cytidine deaminase under conditions in which 1-beta-D-arabinofuranosylcytosine was degraded rapidly to 1-beta-D-arabinofuranosyluracil.
通过对右旋糖酐的氧化，以及氧化右旋糖酐与二氨基烷烃反应形成的希夫碱的还原，制备了几种引入二氨基烷烃的右旋糖酐，并对其作为药物载体进行了评价。制备了N4-(4-羧基buryryl)-1- β - d -阿拉伯糖醛酸胞嘧啶(glu-ara-C)与这些药物载体的偶联物，并对选定的偶联物进行了体内检测，考察了其对胞苷脱氨酶的抑制作用。通过对BDF1小鼠的化学特性和毒性评价，发现在10%氧化条件下制备的乙二胺引入葡聚糖是最有用的药物载体。从葡萄糖-ara-C和乙二胺引入的葡聚糖2000中获得的结合物在携带L1210白血病细胞的BDF1小鼠中显示出很高的抗肿瘤活性，在相对较低的剂量为100 mg当量ara-C/kg时显著。在1- β - d -阿拉伯糖醛酸胞嘧啶快速降解为1- β - d -阿拉伯糖醛酸胞嘧啶的条件下，葡萄糖-阿拉- c和缀合物不受胞苷脱氨酶的影响。
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
