title: Discovery and structural modification of inhibitors of methionine aminopeptidases from Escherichia coli and Saccharomyces cerevisiae.
abstract: A series of pyridine-2-carboxylic acid derivatives were synthesized according to the leads from the screening, and potent inhibitors have been obtained by structural modification. They have shown submicromolar inhibition of the enzymes (for example, for 9n, IC(50) = 130 nM for EcMetAP1 and IC(50) = 380 nM for ScMetAP1). They represent small-molecule MetAP inhibitors with novel structures different from alkylating fumagillin derivatives and peptidic bestatin-based MetAP inhibitor.
authors.affiliation: Chinese National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Life Sciences, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Qun-Li
authors.initials: QL
authors.lastname: Luo
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Li
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Liu
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qian
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Lushington
authors.forename: Qi-Zhuang
authors.initials: QZ
authors.lastname: Ye
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Nan
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D063208:Methionyl Aminopeptidases; D008958:Models, Molecular; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; D013844:Thiazoles; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases