Nastruzzi C, Feriotto G, Spandidos D, Ferroni R, Guarneri M, Barbieri R, Gambari R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
Clin Exp Metastasis. 1989 Jan-Feb;7(1):25-39. doi: 10.1007/BF02057179.
Aromatic polyamidines containing two, three or four benzamidine residues inhibit proteinase activity and proliferation of different human tumor cell lines, including leukemic (K562, HEL), melanoma (Colo 38) and B-lymphoid (WI-L2) cell lines. In addition, the benzamidine derivatives analysed in the present study inhibit cell growth of the Chinese hamster FHO6T1-1 cell line, obtained after transfection of primary lung cells with the activated human T24-Ha-ras-1 oncogene. After treatment of FHO6T1-1 cells with benzamidine derivatives, a sharp decrease of the content of Ha-ras-1 mRNA was found, but not of transferrin receptor mRNA. We found that inhibition of cell proliferation by tetra-benzamidine derivatives is not restricted to tumor cells, but concerns also non-tumorigenic cell lines as well as normal primary fibroblasts. Therefore, our analysis was extended to di- and tri-benzamidine derivatives, which could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors. The data obtained demonstrate that these latter compounds and their halo-derivatives also exhibit strong antiproliferative effects on in vitro cultured cells.
含有两个、三个或四个苯甲脒残基的芳香族聚脒可抑制蛋白酶活性以及不同人类肿瘤细胞系的增殖，这些细胞系包括白血病细胞系（K562、HEL）、黑色素瘤细胞系（Colo 38）和B淋巴细胞系（WI-L2）。此外，本研究中分析的苯甲脒衍生物可抑制中国仓鼠FHO6T1-1细胞系的细胞生长，该细胞系是原代肺细胞用激活的人类T24-Ha-ras-1癌基因转染后获得的。用苯甲脒衍生物处理FHO6T1-1细胞后，发现Ha-ras-1 mRNA的含量急剧下降，但转铁蛋白受体mRNA的含量未下降。我们发现，四苯甲脒衍生物对细胞增殖的抑制作用不仅限于肿瘤细胞，也涉及非致瘤细胞系以及正常原代成纤维细胞。因此，我们的分析扩展到二苯甲脒和三苯甲脒衍生物，它们可被用作合成药物偶联单克隆抗体或生长因子的有用底物。获得的数据表明，这些后一种化合物及其卤代衍生物对体外培养的细胞也表现出强烈的抗增殖作用。
