A series of quinoline analogues as potent inhibitors of C. albicans prolyl tRNA synthetase.
A series of quinoline inhibitors of C. albicans prolyl tRNA synthetase was identified. The most potent analogue, 2-(4-bromo-phenyl)-6-chloro-8-methyl-4-quinolinecarboxylic acid, showed IC50 = 5 nM (Ca. ProRS) with high selectivity over the human enzyme.
Yu
X Y
XY
Department of Medicinal Chemistry, Cubist Pharmaceuticals, Inc., Cambridge, MA 02139, USA. xiang@cubist.com
Hill
J M
JM
Yu
G
G
Yang
Y
Y
Kluge
A F
AF
Keith
D
D
Finn
J
J
Gallant
P
P
Silverman
J
J
Lim
A
A
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012361:RNA, Transfer, Pro / Q000096:biosynthesis*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011804:Quinolines; D012361:RNA, Transfer, Pro; D000604:Amino Acyl-tRNA Synthetases