Miyanaga Satoshi, Sakurai Hiroaki, Saiki Ikuo, Onaka Hiroyasu, Igarashi Yasuhiro
Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Bioorg Med Chem. 2009 Apr 1;17(7):2724-32. doi: 10.1016/j.bmc.2009.02.040. Epub 2009 Feb 25.
Myxochelin A (1) is an inhibitor of tumor cell invasion produced by the bacterium belonging to the genus Nonomuraea. In order to obtain more potent inhibitors, a series of myxochelin analogues [2 and (S)-3-17] were synthesized through the coupling of lysine or diaminoalkane derivatives and appropriately protected hydroxybenzoate, 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. Among the synthetic analogues tested, compound (S)-6 which possesses carbamoyl group at C-1 was found to be the most potent antiinvasive agent and is considered to be a promising lead molecule for the antimetastasis. Compound (S)-6 was also shown to inhibit gelatinase activities of MMP-2 and MMP-9 and in vivo lung metastasis in mice.
粘杆菌素A（1）是一种由野野村菌属细菌产生的肿瘤细胞侵袭抑制剂。为了获得更有效的抑制剂，通过赖氨酸或二氨基烷烃衍生物与适当保护的羟基苯甲酸酯偶联，然后进行官能团修饰和脱保护，合成了一系列粘杆菌素类似物[2和（S）-3-17]。评估了这些化合物对小鼠结肠26-L5癌细胞侵袭的抑制活性。在所测试的合成类似物中，在C-1位具有氨基甲酰基的化合物（S）-6被发现是最有效的抗侵袭剂，被认为是抗转移的有前途的先导分子。化合物（S）-6还显示出抑制MMP-2和MMP-9的明胶酶活性以及小鼠体内的肺转移。
