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) < 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.
Nemoto
H
H
Department of Applied Molecular Science, Okazaki Institute for Molecular Science, Japan.
Cai
J
J
Asao
N
N
Iwamoto
S
S
Yamamoto
Y
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001896:Boron Compounds / Q000737:chemistry*; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D001896:Boron Compounds; D014867:Water; D010649:Phenylalanine; C033685:4-boronophenylalanine