Chemical modification of the beta-glucocerebrosidase inhibitor N-octyl-beta-valienamine: synthesis and biological evaluation of 4-epimeric and 4-O-(beta-D-galactopyranosyl) derivatives.
N-Octyl-beta-valienemine (1), a potent beta-glucocerebrosidase inhibitor, was chemically transformed into two biologically interesting compounds: the 4-epimer, beta-galacto-type N-octyl-valienamine, and the 4-O-(beta-D-galactopyranosyl) derivative, a carba-lactosylceramide analogue. The former, interestingly, could be demonstrated to act as a very effective inhibitor (IC(50)=0.3 microM) of human beta-galactosidase. The latter exhibited moderate inhibitory activity (IC(50)=20 microM) against beta-glucocerebrosidase (mouse liver).
Ogawa
Seiichiro
S
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, 223-8522, Yokohama, Japan. ogawa@applc.keio.ac.jp
Matsunaga
Yuko Kobayashi
YK
Suzuki
Yoshiyuki
Y
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006595:Hexosamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D006595:Hexosamines; C116532:N-octyl-beta-valienamine; D001616:beta-Galactosidase; D005962:Glucosylceramidase