Aleksander S K, Liashenko V A, Iakushkina I V
Antibiotiki. 1981 Apr;26(4):298-302.
Bovine serum albumin (BSA) and carminomycin, an anthracycline antibiotic, were subjected to conjugation with glutaraldehyde and their complexes with various contents of the antibiotic were prepared. The molar ratios of carminomycin and BSA were 8:1, 4:1, and 2:1. The antitumor effect of the preparations was studied on the models of mouse transplantable lymphosarcoma LIO equal 1 and ascitic forms of mouse lymphadenosis NK/Ly in vivo and in vitro. Their immunodepressant effect was evaluated from the decrease in the hemagglutinin titers in the mice immunized with sheep red blood cells. It was shown that when the toxicity of the complexes was the same, their antitumor and immunodepressant activities were different. The therapeutic activity of carminomycin in the four- and eight-substituted complexes was much higher than that of carminomycin alone. It is suggested that the differences in the activity of the complexes were connected with differences in their pharmacokinetics. It was found that the chemotherapeutic properties of the complexes may have changed by variation of the number of the cytostatic residues in the albumin molecule. The findings indicate that the whole complex molecule interacts with the malignant cell and not carminomycin preliminarily detached from it.
将牛血清白蛋白(BSA)与一种蒽环类抗生素卡米诺霉素用戊二醛进行偶联,制备了含有不同抗生素含量的复合物。卡米诺霉素与BSA的摩尔比分别为8:1、4:1和2:1。在小鼠可移植性淋巴肉瘤LIO等于1的模型以及小鼠淋巴腺病NK/Ly腹水型模型上,对这些制剂的体内外抗肿瘤作用进行了研究。从用绵羊红细胞免疫的小鼠血凝素滴度降低情况评估它们的免疫抑制作用。结果表明,当复合物的毒性相同时,它们的抗肿瘤和免疫抑制活性不同。卡米诺霉素在四取代和八取代复合物中的治疗活性远高于单独使用卡米诺霉素时。提示复合物活性的差异与它们的药代动力学差异有关。发现通过改变白蛋白分子中细胞生长抑制剂残基的数量,复合物的化疗性质可能发生了改变。研究结果表明,整个复合物分子与恶性细胞相互作用,而不是卡米诺霉素先从复合物中分离出来再与细胞相互作用。