TY - JOUR
T1 - Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry
AU - Elías-Rodríguez, Pilar
AU - Pingitore, Valeria
AU - Carmona, Ana T.
AU - Moreno-Vargas, Antonio J.
AU - Ide, Daisuke
AU - Miyawaki, Shota
AU - Kato, Atsushi
AU - Álvarez, Eleuterio
AU - Robina, Inmaculada
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/8/17
Y1 - 2018/8/17
N2 - The parallel synthesis of a 26-membered-library of aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α-galactosidases has been carried out. The combination of the (thio)urea-forming click reaction and the in situ screening is pioneer in the search for glycosidase inhibitors and has allowed the discovery of a potent coffee bean α-galactosidase inhibitor (IC50 = 0.37 μM, Ki = 0.12 μM) that has also showed inhibition against human lysosomal α-galactosidase (α-Gal A, IC50 = 5.3 μM, Ki = 4.2 μM).
AB - The parallel synthesis of a 26-membered-library of aromatic/aliphatic-(thio)urea-linked pyrrolizidines followed by in situ biological evaluation toward α-galactosidases has been carried out. The combination of the (thio)urea-forming click reaction and the in situ screening is pioneer in the search for glycosidase inhibitors and has allowed the discovery of a potent coffee bean α-galactosidase inhibitor (IC50 = 0.37 μM, Ki = 0.12 μM) that has also showed inhibition against human lysosomal α-galactosidase (α-Gal A, IC50 = 5.3 μM, Ki = 4.2 μM).
UR - http://www.scopus.com/inward/record.url?scp=85050226238&partnerID=8YFLogxK
U2 - 10.1021/acs.joc.8b01073
DO - 10.1021/acs.joc.8b01073
M3 - 学術論文
C2 - 30014697
AN - SCOPUS:85050226238
SN - 0022-3263
VL - 83
SP - 8863
EP - 8873
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 16
ER -