CELLULAR PHARMACODYNAMICS OF SEVERAL ANTHRACYCLINE ANTIBIOTICS
CELLULAR PHARMACODYNAMICS OF SEVERAL ANTHRACYCLINE ANTIBIOTICS
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DOI：
10.1021/jm00227a015
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发表时间：
1976-01-01
影响因子：
7.3
通讯作者：
HILDEBRAND, RC
中科院分区：
文献类型：
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作者：
BACHUR, NR;STEELE, M;HILDEBRAND, RC
蒽环类抗生素阿霉素和柔红霉素C-9侧链的改变对培养的L1210小鼠白血病细胞对抗生素的摄取和积累有深远的影响。L1210细胞对DNA和RNA生物合成的抑制程度与细胞对药物类似物的摄取和积累直接相关。药物的极性代谢物柔红霉素和阿霉素对核酸代谢仍有抑制作用，但降低了膜结合力和通透性。细胞对C-9类似物的摄取和积累与药物的极性成反比。蒽环类化合物的极性通过对膜通透性、代谢和大分子结合的基本影响而导致治疗指数和体内活性的差异。
Alterations in the C-9 side chain of the anthracycline antibiotics, adriamycin and daunorubicin, have a profound effect on antibiotic uptake and accumulation by cultured L1210 mouse leukemia cells. The degree of inhibition of DNA and RNA biosynthesis in the L1210 cells is directly related to the cellular uptake and accumulation of the drug analogs. Polar drug metabolites, daunorubicinol and adriamycinol, retain inhibitory activity against nuclei acid metabolism, but have decreased membrane binding and permeability. Cellular uptake and accumulation of the C-9 analogs are inversely related to drug polarity. The polarity of the anthracycline analogs contributes to the differences in therapeutic index and in vivo activity through fundamental effects on membrane permeability, metabolism and macromolecular binding.