SYNTHESIS AND ANTITUMOR-ACTIVITY OF ALPHA-1,4-POLYGALACTOSAMINE AND N-ACETYL-ALPHA-1,4-POLYGALACTOSAMINE IMMOBILIZED 5-FLUOROURACILS THROUGH HEXAMETHYLENE SPACER GROUPS VIA UREA, UREA BONDS

被引：20

作者：

OHYA, Y

HUANG, TZ

OUCHI, T

HASEGAWA, K

TAMURA, J

KADOWAKI, K

MATSUMOTO, T

SUZUKI, S

SUZUKI, M

机构：

[1] Research Laboratory, Higeta Shoyu Co. Ltd., Choshi, Chiba

[2] Department of Microbiology, The Second Department of Hygienic Chemistry, Tohoku College of Pharmacy, Sendai, Miyagi

来源：

JOURNAL OF CONTROLLED RELEASE | 1991年 / 17卷 / 03期

关键词：

5-FLUOROURACIL; ALPHA-1,4-POLYGALACTOSAMINE; GALACTOSAMINO-OLIGOSACCHARIDE; CONJUGATE; ANTITUMOR ACTIVITY;

D O I：

10.1016/0168-3659(91)90144-3

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In order to provide a macromolecular prodrug of 5-fluorouracil (5FU) with reduced side-effects, having an affinity for tumor cells and exhibiting strong antitumor activity, the covalent attachment of 5FUs to alpha-1,4-polygalactosamine (PGA), N-acetyl-alpha-1,4-polygalactosamine (NAPGA) and their oligomers (GOS, NAGOS) through hexamethylene spacer groups via urea, urea bonds was carried out. The survival effect against p388 lymphocytic leukemia in female CDF1 mice by intraperitoneal (ip) transplantation/ip injection in vivo and the growth-inhibitory effect on Meth-A fibrosarcoma in male BALB/c SPF mice by subcutaneous (sc) implantation/intravenous (iv) injection in vivo were evaluated. The effects of the degree of substitution of 5FU based on the number of galactosamine groups and the degree of N-acetylation of amino groups of PGA based on the number of galactosamine groups on prolongation of life were investigated. The PGA/5FU and NAPGA/5FU conjugates exhibited strong survival effects against p388 lymphocytic leukemia and the GOS/5FU conjugate showed significant growth-inhibitory effect on Meth-A fibrosarcoma. The obtained PGA/5FU, NAPGA/5FU, GOS/5FU and NAGOS/5FU conjugates did not display any acute toxicity even in the high dose ranges.

引用

页码：259 / 266

页数：8

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