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(1 S ,2 S ,3 R ,6 R )‐6‐Aminocyclohex‐4‐ene‐1,2,3‐triol (= (−)‐Conduramine B‐1) Is a Selective Inhibitor of α ‐Mannosidases. Its Inhibitory Activity Is Enhanced by N ‐Benzylation
Author(s) -
Łysek Robert,
Schütz Catherine,
Vogel Pierre
Publication year - 2005
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200590220
Subject(s) - chemistry , iminosugar , mannosidase , stereochemistry , glucosidases , potency , inhibitory postsynaptic potential , ic50 , enzyme , biochemistry , in vitro , neuroscience , biology
(−)‐ and (+)‐Conduramine B‐1 ((−)‐ and (+)‐ 5 , resp.) have been derived from (+)‐ and (−)‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐one (‘naked sugars’ of the first generation). Although (−)‐ 5 imitates the structure of β ‐glucosides, it does not inhibit β ‐glucosidases but inhibits α ‐mannosidases selectively. N ‐Benzylation of (−)‐ 5 improves the potency of conduramine B‐1 as α ‐mannosidase inhibitor and also generates compounds inhibiting β ‐glucosidases. For instance, (−)‐ N ‐benzyl‐conduramine B‐1 ((−)‐ 19a ) is a competitive inhibitor of β ‐glucosidase from almonds ( IC 50 = 32 μ M , K i = 10 μ M ) and a weak inhibitor of α ‐mannosidases from jack bean ( IC 50 = 171 μ M ) and from almonds ( IC 50 = 225 μ M ) whereas (−)‐ N ‐(4‐phenylbenzyl)conduramine B‐1 ((−)‐ 19g ) is a good inhibitor of α ‐mannosidase from jack beans ( IC 50 = 29 μ M , K i = 4.8 μ M ) and a weaker inhibitor of β ‐glucosidase from almonds ( IC 50 = 32 μ M , K i = 7.8 μ M ) ( Table 1 ).