AMINO-ACID AND DIPEPTIDE DERIVATIVES OF DAUNORUBICIN .2. CELLULAR PHARMACOLOGY AND ANTI-TUMOR ACTIVITY ON L1210 LEUKEMIC-CELLS INVITRO AND INVIVO
AMINO-ACID AND DIPEPTIDE DERIVATIVES OF DAUNORUBICIN .2. CELLULAR PHARMACOLOGY AND ANTI-TUMOR ACTIVITY ON L1210 LEUKEMIC-CELLS INVITRO AND INVIVO
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多柔比星的氨基酸和二肽衍生物 .2. 细胞药理学及对 L1210 白血病细胞的体外和体内抗肿瘤活性
DOI：
10.1021/jm00185a004
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发表时间：
1980-01-01
影响因子：
7.3
通讯作者：
TROUET, A
中科院分区：
文献类型：
--
作者：
BAURAIN, R;MASQUELIER, M;TROUET, A
本文研究了柔红霉素（DNR）的氨基酸和二肽衍生物在小鼠白血病L1210细胞上的体外蓄积。只有Leu-DNR达到接近DNR的蓄积水平，而Val-DNR、Ile-DNR和Leu-Leu-DNR达到中间值。当L210细胞与DNR、Leu-Leu-DNR、Leu-Ala-DNR和Leu-DNR共同孵育时，发现细胞内存在DNR。衍生物在体外对L1210细胞的细胞生长抑制活性与其摄取或转化为柔红霉素无关。在等毒性剂量下，对静脉注射接种的L1210白血病进行静脉注射给药，所有衍生物的活性均低于DNR。在皮下注射时。Leu-DNR、Ala-Leu-DNR和Leu-Leu-DNR比DNR活性高得多，ILS显著增加，肿瘤进展减少。这些化合物的优越性可能是由于它们更大的疏水性和它们被肿瘤细胞分泌的或存在于肿瘤细胞表面上的酶原位水解。
The accumulation of amino acid and dipeptide derivatives of DNR (daunorubicin) was studied in vitro on mouse leukemia L1210 cells. Only Leu-DNR reached accumulation levels close to DNR, while Val-DNR, Ile-DNR and Leu-Leu-DNR reach intermediate values. Intracellular DNR was found when the L210 cells were incubated in the presence of DNR, Leu-Leu-DNR, Leu-Ala-DNR and Leu-DNR. The cytostatic activity of the derivatives in vitro on L1210 cells cannot be correlated with their uptake or conversion into DNR. At equitoxic doses given i.v. on the i.v. inoculated form of L1210 leukemia, all the derivatives are less active than DNR. When given i.v. on the s.c. inoculated L120 leukemia, Leu-DNR, Ala-Leu-DNR and Leu-Leu-DNR are much more active than DNR with a striking increase in ILS and reduction of tumor progression. The superiority of those compounds could be due to their greater hydrophobicity and to their hydrolysis in situ by enzymes secreted by tumor cells or present on the tumor cells surface.