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Synthesis, Characterization, and Antileukemic Properties of Naphthoquinone Derivatives of Lawsone
Author(s) -
Inagaki Ryuta,
Ninomiya Masayuki,
Tanaka Kaori,
Koketsu Mamoru
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500189
Subject(s) - lawsone , naphthoquinone , chemistry , 1,4 naphthoquinone , cytotoxicity , glutathione , plumbagin , stereochemistry , combinatorial chemistry , biochemistry , organic chemistry , in vitro , biology , enzyme , genetics
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.