School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhua Xilu, Jinan 250012, Shandong Province, PR China.
Bioorg Med Chem Lett. 2011 Feb 15;21(4):1089-91. doi: 10.1016/j.bmcl.2010.12.133. Epub 2011 Jan 4.
Brartemicin is a trehalose-based inhibitor of tumor cell invasion produced by the actinomycete of the genus Nonomuraea. In order to explore the preliminary structure-activity relationship and obtain more potent inhibitors, a series of brartemicin analogs were synthesized through the Mitsunobu coupling of the secondary hydroxyls benzyl protected α,α-D-trehalose with benzoic acid derivatives, followed by modification of functional groups and deprotection. These compounds were evaluated for their inhibitory activity against invasion of murine colon 26-L5 carcinoma cells in vitro. Among the synthetic analogs tested, 6,6'-bis(2,3-dimethoxybenzoyl)-α,α-D-trehalose (5e) was found to be the most potent anti-invasive agent, exhibited a 2.6-fold improvement with regard to the parent natural product brartemicin, and it is considered to be a promising lead molecule for the anti-metastasis.
布瑞替丁是由游动放线菌诺卡氏菌属产生的一种基于海藻糖的肿瘤细胞侵袭抑制剂。为了探索初步的结构-活性关系并获得更有效的抑制剂，通过苯甲酰基保护的α,α-D-海藻糖的仲羟基与苯甲酸衍生物的 Mitsunobu 偶联，随后进行官能团修饰和脱保护，合成了一系列布瑞替丁类似物。这些化合物在体外评估了对小鼠结肠 26-L5 癌细胞侵袭的抑制活性。在所测试的合成类似物中，6,6'-双(2,3-二甲氧基苯甲酰基)-α,α-D-海藻糖（5e）被发现是最有效的抗侵袭剂，与天然产物布瑞替丁相比，活性提高了 2.6 倍，被认为是一种有前途的抗转移的先导分子。
