Synthesis and biological evaluation of 2-amino-2-deoxy- and 6-amino-6-deoxy-cyclomaltoheptaose polysulfates as synergists for angiogenesis inhibition.
2-Amino-2-deoxy-cyclomaltoheptaose was prepared from beta-cyclodextrin perbenzoate [heptakis(2,3,6-tri-O-benzoyl)cyclomaltoheptaose] by a series of reactions including selective de-O-benzoylation at C-2 of one of the perbenzoylated D-glucopyranosyl moieties, oxidation to the 2-ulose derivative, oxime formation, and reduction to the 2-amino-2-deoxy-D-glucose moiety. This compound and 6-amino-6-deoxycyclomaltoheptaose accessible from beta-cyclodextrin through the known procedure were sulfated to give polysulfated aminocyclomaltoheptaose derivatives (3, 5). Employing beta-cyclodextrin polysulfate as a reference compound, the synergistic effects of 3 and 5 for cortexolone or angiogenesis inhibitory activity were examined by rabbit-corneal micropocket assay system. In contrast to the significant anti-angiogenesis activity of the beta-cyclodextrin polysulfate-cortexolone pair, neither 3 nor 5 showed any cooperative activity with cortexolone in the inhibition of basic FGF-induced angiogenesis.
Sakairi
N
N
Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Kuzuhara
H
H
Okamoto
T
T
Yajima
M
M
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D003350:Cortodoxone / Q000494:pharmacology; D003505:Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004357:Drug Synergism; D005121:Extremities / Q000098:blood supply; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013997:Time Factors
C105407:2-amino-2-deoxycyclomaltoheptaose heptadecasulfate; C105408:6-amino-6-deoxycyclomaltoheptaose octadecasulfate; D003505:Cyclodextrins; C105409:cyclomaltoheptaose heptadecasulfate; D016222:Fibroblast Growth Factor 2; D003350:Cortodoxone