title: Synthesis, Characterization, and Antileukemic Properties of Naphthoquinone Derivatives of Lawsone.
abstract: Naphthoquinones are considered privileged structures for anticancer drug molecules. The Heck reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with 1-bromo-3-methyl-2-butene offered easy access to lapachol. Several naturally occurring linear and angular heterocyclic quinoids (α-lapachone, β-lapachone, dunnione, and related analogues) were prepared from lapachol. Furthermore, we demonstrated that the synthetic naphthoquinones inhibit cell proliferation in human leukemia HL-60 cells. In particular, angular-type derivatives were found to possess moderate cytotoxicity and to elevate the levels of intracellular glutathione disulfide (GSSG). Our work highlights the significant potential of naturally occurring angular-series naphthoquinones as antileukemic agents.
authors.affiliation: Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan).
authors.forename: Ryuta
authors.initials: R
authors.lastname: Inagaki
authors.affiliation: Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan).|Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan).
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ninomiya
authors.affiliation: Division of Anaerobe Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1194 (Japan).|United Graduate School of Drug Discovery and Medicinal Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194 (Japan).
authors.forename: Kaori
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan). koketsu@gifu-u.ac.jp.|Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan). koketsu@gifu-u.ac.jp.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D019281:Dimerization; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D008968:Molecular Conformation; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D000970:Antineoplastic Agents; D009285:Naphthoquinones; C474009:dunnione; C014638:beta-lapachone; C008252:lapachol; D005978:Glutathione; C021639:2-butene; C005090:lawsone
keywords: antileukemic activity; glutathione; lapachol; natural products; quinones