Lethal toxicity and adjuvant activities of synthetic TDM and its related compounds in mice.
Lethal toxicity and adjuvant activities of synthetic TDM and its related compounds in mice.
复制标题
合成 TDM 及其相关化合物对小鼠的致死毒性和佐剂活性。
DOI：
10.1016/0264-410x(89)90242-9
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发表时间：
1989
期刊：
影响因子：
5.5
通讯作者：
I. Azuma
中科院分区：
文献类型：
--
作者：
T. Sakurai;I. Saiki;H. Ishida;K. Takeda*;I. Azuma
合成了海藻糖-6，6 ′-二霉菌酸酯（TDM）及其单糖型类似物，并对它们的致死活性和佐剂活性进行了研究。所有具有葡萄糖或N-乙酰葡糖胺部分的单糖型类似物对小鼠没有致死毒性;特别是，d-GlcNAcM（1-脱氧）和d-GlcNM作为9%水包油乳剂静脉给药后，在早期阶段没有引起任何体重减轻。腹膜内给药d-GlcNAcM（1-脱氧）的水悬浮液，以及TDM，可以激活巨噬细胞成为杀肿瘤细胞对肿瘤细胞，而-GlcNAcM（1-脱氧）的油乳剂，不像TDM，在静脉注射后，在肺中没有引起肉芽肿形成。当瘤内给药两次时，角鲨烷处理的dd-GlcNAcM（1-脱氧）显示出对B16-BL 6黑色素瘤细胞自发性肺转移的显着抑制。TDM的无毒单糖型类似物[d-GlcNAcM（1-deoxy）]是激活巨噬细胞和预防癌症转移的有益佐剂。
Trehalose-6,6′-dimycolate (TDM) and its monosaccharide-type analogues were synthesized, and their lethal and adjuvant activities were examined in mice. All the monosaccharide-type analogues with a glucose orN-acetylglucosamine moiety were devoid of lethal toxicity to mice; in particular,d-GlcNAcM(1-deoxy) andd-GlcNM did not cause any loss of body weight at an early stage after intravenous administration as a 9% oil-in-water emulsion. Intraperitoneal administration ofd-GlcNAcM(1-deoxy) in aqueous suspension, as well as TDM, could activate macrophages to become tumoricidal against tumour cells, whereasd-GlcNAcM(1-deoxy) in oil emulsion, unlike TDM, caused no granulomatous formation in the lung after intravenous injection. Squalane-treatedd-GlcNAcM(1-deoxy) showed significant inhibition of spontaneous lung metastases by B16-BL6 melanoma cells when it was administered twice intratumorally. The non-toxic monosaccharide-type analogue of TDM [d-GlcNAcM(1-deoxy)] was a beneficial adjuvant for the activation of macrophages and the prevention of cancer metastasis.