Synthesis and antitumor activities of novel 5-deazaflavin-sialic acid conjugate molecules.
6-Nitro-5-deazaflavin derivatives bearing O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha- and beta-D-galacto-non-2-ulopyranosylonate)alkyl group (sialosylalkyl group) at N(3) or N(10) and 8-amino-5-deazaflavin substituted with the sialosylalkyl group at the amino group were synthesized and their physicochemical properties as well as antitumor effects on KB and L1210 cells have been investigated. The configurations of the glycosides were determined by 1H NMR and rate of hydrolysis of the glycosidic bond. It has been found that these conjugate molecules show significant antitumor activities. Combination of an 8-amino-5-deazaflavin with the sialosylalkyl group have been found to give rise to significant increase in antitumor activities of the compound. Antitumor effects of 6-nitro-5-deazaflavin-sialic acid conjugate molecules were similar or rather weak in comparison with those of the 6-nitro-5-deazaflavin derivatives without sialosylalkyl group.
Ikeuchi
Y
Y
Faculty of Pharmaceutical Sciences, Kyoto University, Japan. ikeuchi@snowbrand.co.jp
Sumiya
M
M
Kawamoto
T
T
Akimoto
N
N
Mikata
Y
Y
Kishigami
M
M
Yano
S
S
Sasaki
T
T
Yoneda
F
F
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002942:Circular Dichroism; D004354:Drug Screening Assays, Antitumor; D005415:Flavins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells; D007939:Leukemia L1210; D051379:Mice; D015394:Molecular Structure; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D005415:Flavins; D012794:Sialic Acids