title: Synthesis of NAG-thiazoline-derived inhibitors for β-N-acetyl-d-hexosaminidases.
abstract: β-N-Acetyl-d-hexosaminidases are responsible for the metabolism of glycoconjugates in diverse physiological processes that are important targets for medicine and pesticide development. Fourteen new NAG-thiazoline derivatives were synthesized by cyclization and click reaction using d-glucosamine hydrochloride as the starting material. All the compounds created were characterized by NMR and HRMS spectra. A preliminary bioassay, using four enzymes from two β-N-acetyl-d-hexosaminidase families, showed that most of the compounds synthesized exhibit selective inhibition of GH84 β-N-acetyl-d-hexosaminidase. Among the compounds tested, compounds 5a (IC50=12.6 μM, hOGA) and 5e (IC50=12.5 μM, OfOGA) proved to be a highly selective and potent inhibitor.
authors.affiliation: Key Lab of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Hanchu
authors.initials: H
authors.lastname: Kong
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Lab of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. Electronic address: luhz@cau.edu.cn.
authors.forename: Huizhe
authors.initials: H
authors.lastname: Lu
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Lab of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Key Lab of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
authors.forename: Daoquan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Lab of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. Electronic address: zhangjianjun@cau.edu.cn.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007915:Lepidoptera / Q000201:enzymology; D013379:Substrate Specificity; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D013844:Thiazoles; D001619:beta-N-Acetylhexosaminidases; C487818:N-acetylglucosamine thiazoline; D000117:Acetylglucosamine
keywords: NAG-thiazoline derivatives; Selective inhibitors; Synthesis; β-N-Acetyl-d-hexosaminidases