Concise synthesis of a probe molecule enabling analysis and imaging of vizantin.
Concise synthesis of a probe molecule enabling analysis and imaging of vizantin.
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DOI：
10.1248/cpb.c13-00006
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发表时间：
2013-04
影响因子：
1.7
通讯作者：
Hirofumi Yamamoto;M. Oda;Mayo Nakano;Kenta Yabiku;M. Shibutani;Toshiyuki Nakanishi;Midori Suenaga;Masahisa Inoue;H. Imagawa;M. Nagahama;Y. Matsunaga;S. Himeno;K. Setsu;J. Sakùrai;M. Nishizawa*
中科院分区：
文献类型：
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作者：
Hirofumi Yamamoto;M. Oda;Mayo Nakano;Kenta Yabiku;M. Shibutani;Toshiyuki Nakanishi;Midori Suenaga;Masahisa Inoue;H. Imagawa;M. Nagahama;Y. Matsunaga;S. Himeno;K. Setsu;J. Sakùrai;M. Nishizawa*
海藻糖6，6 '-二谷米霉酸酯（TDCM）于1963年首次被鉴定为棒状杆菌属的细胞表面糖脂。由Ioneda和同事们。TDCM由于其免疫佐剂性质而显示出有效的抗肿瘤活性。此外，TDCM在小鼠中的毒性远弱于相关的分枝菌酸海藻糖二酯;海藻糖6，6 '-二分枝菌酸酯（TDM，以前称为脐带因子）。我们已经研究了这类化合物的化学修饰，以产生新的药剂，其显示出增加的免疫佐剂活性，同时具有最小的相关毒性。在这项工作的过程中，我们最近开发了6，6 '-双-O-（3-壬基十二烷酰基）-α，α'-海藻糖（命名为vizantin）。我们的研究结果表明，vizantin对B16-F0黑色素瘤细胞的实验性肺转移表现出有效的预防作用，而没有小鼠体重减轻和死亡。此外，vizantin在体外模型中有效刺激人巨噬细胞，使其成为临床应用中安全佐剂的有希望的候选者。为了阐明维赞汀的药代动力学，在对维赞汀进行构效关系（SAR）研究的基础上，开发了具有相似活性的探针分子。通过宏观共聚焦显微镜评估静脉内施用到小鼠中后探针分子的分布，其中发现其在肺和肝中积累。
Trehalose 6,6'-dicorynomycolate (TDCM) was first characterized in 1963 as a cell surface glycolipid of Corynebacterium spp. by Ioneda and co-workers. TDCM shows potent anti-tumor activity due to its immunoadjuvant properties. Furthermore, the toxicity of TDCM in mice is much weaker than the related trehalose diester of mycolic acid; trehalose 6,6'-dimycolate (TDM, formerly known as cord factor). We have investigated the chemical modification of this class of compound to generate novel agents that display increased immunoadjuvant activity with minimal associated toxicity. During the course of this work we recently developed 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose (designated as vizantin). Our results show that vizantin exhibited a potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells without a loss of body weight and death in mice. Furthermore, vizantin effectively stimulated human macrophages in an in vitro model, making it a promising candidate for a safe adjuvant in clinical applications. In order to elucidate the pharmacokinetics of vizantin, a probe molecule with similar activity was developed on the basis of a structure-activity relationship (SAR) study with vizantin. The distribution of the probe molecule after intravenous administration into a mouse was assessed by macro confocal microscopy, where it was found to accumulate in the lungs and liver.