SYNTHESIS AND BIOLOGICAL PROPERTIES OF WATER-SOLUBLE P-BORONOPHENYLALANINE DERIVATIVES - RELATIONSHIP BETWEEN WATER SOLUBILITY, CYTOTOXICITY, AND CELLULAR UPTAKE

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) less than or equal to BPA(OH)(2) < BPA(OH)(4). Cytotoxicity to B-16 melanoma and TIG hybrobrast cells decreased in the order of BPA >> BPA(OH) greater than or equal to BPA(OH)(2) > BPA(OH)(4). The cellular uptake by both B-16 and TIG cells decreased in the order of BPA >> BPA(OH) greater than or equal to BPA(OH)2 > BPA(OH)4, whereas the uptake ratio of B-16/TIG increased in the order of BPA < BPA(OH) less than or equal to BPA(OH)(2) < BPA(OH)(4). The latter ratio indicates the selectivity on the uptake by a cancer to normal cell.