NMR Biochemical Assay for Oxidosqualene Cyclase: Evaluation of Inhibitor Activities on Trypanosoma cruzi and Human Enzymes

Autor:	Shusaku Mizukami, Osamu Tani, Yukihiro Tateishi, Kazuhiko Yamasaki, Takayuki Suzuki, Tatsuya Niimi, Yukie Akutsu, Tetsuo Yanagi, Tomomi Kubota, Shinji Ito, Ichiji Namatame, Tomohiko Yamaguchi, Yasunori Chiba, Koji Furukawa, Kenji Hirayama, Hitoshi Sakashita
Rok vydání:	2018
Předmět:	0301 basic medicine Chagas disease Trypanosoma cruzi 010402 general chemistry 01 natural sciences Oxidosqualene cyclase 03 medical and health sciences Inhibitory Concentration 50 Drug Discovery medicine Humans Enzyme Inhibitors Sterol biosynthesis Intramolecular Transferases Nuclear Magnetic Resonance Biomolecular chemistry.chemical_classification biology Chemistry Drug discovery Assay biology.organism_classification medicine.disease 0104 chemical sciences 030104 developmental biology Enzyme Biochemistry Molecular Medicine
Zdroj:	Journal of medicinal chemistry. 61(11)
ISSN:	1520-4804
Popis:	Oxidosqualene cyclase (OSC), a membrane-associated protein, is a key enzyme of sterol biosynthesis. Here we report a novel assay for OSC, involving reaction in aqueous solution, NMR quantification in organic solvent, and factor analysis of spectra. We evaluated one known and three novel inhibitors on OSC of Trypanosoma cruzi, a parasite causative of Chagas disease, and compared their effects on human OSC for selectivity. Among them, one novel inhibitor showed a significant parasiticidal activity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d5f661d8d78fdd624c805f90da8058bf https://pubmed.ncbi.nlm.nih.gov/30004699 Zobrazit plný text záznamu