Nemoto H, Cai J, Asao N, Iwamoto S, Yamamoto Y
Department of Applied Molecular Science, Okazaki Institute for Molecular Science, Japan.
J Med Chem. 1995 May 12;38(10):1673-8. doi: 10.1021/jm00010a012.
Water-soluble p-boronophenylalanine (BPA) derivatives having cascade polyols, the monohydroxy derivative BPA(OH) (4), the dihydroxy analogue BPA(OH)2 (5), and the tetrahydroxy analogue BPA(OH)4 (6), were synthesized in order to elucidate a relationship between the molecular structures and the cellular uptake. Biological properties of these compounds in addition to BPA (1) itself were investigated. Water solubility increased in the order of BPA < BPA(OH) < or = BPA(OH)2 > BPA(OH)4. Cytotoxicity to B-16 melanoma and TIG hybrobrast cells decreased in the order of BPA >> BPA(OH) > or = BPA(OH)2 > BPA(OH)4. The cellular uptake by both B-16 and TIG cells decreased in the order of BPA > BPA(OH) > or = BPA(OH)2 > BPA(OH)4, whereas the uptake ratio of B-16/TIG increased in the order of BPA < BPA(OH) < or = BPA(OH)2 < BPA(OH)4. The latter ratio indicates the selectivity on the uptake by a cancer to normal cell.
为阐明分子结构与细胞摄取之间的关系，合成了具有级联多元醇的水溶性对硼苯丙氨酸（BPA）衍生物、单羟基衍生物BPA(OH)（4）、二羟基类似物BPA(OH)2（5）和四羟基类似物BPA(OH)4（6）。除了BPA（1）本身外，还研究了这些化合物的生物学特性。水溶性按BPA < BPA(OH) < 或 = BPA(OH)2 > BPA(OH)4的顺序增加。对B-16黑色素瘤细胞和TIG杂交瘤细胞的细胞毒性按BPA >> BPA(OH) > 或 = BPA(OH)2 > BPA(OH)4的顺序降低。B-16细胞和TIG细胞对其摄取量按BPA > BPA(OH) > 或 = BPA(OH)2 > BPA(OH)4的顺序降低，而B-16/TIG摄取率按BPA < BPA(OH) < 或 = BPA(OH)2 < BPA(OH)4的顺序增加。后一比率表明癌症细胞对正常细胞摄取的选择性。
