Premium
Synthesis and Cytotoxic Activity of a Small Naphthoquinone Library: First Synthesis of Juglonbutin
Author(s) -
Brötz Elke,
Herrmann Jennifer,
Wiese Jutta,
Zinecker Heidi,
Maier Armin,
Kelter Gerhardt,
Imhoff Johannes F.,
Müller Rolf,
Paululat Thomas
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201402272
Subject(s) - chemistry , stereochemistry , alkylation , naphthoquinone , side chain , mode of action , cytotoxic t cell , glycogen synthase , chemical synthesis , gsk 3 , combinatorial chemistry , biochemistry , enzyme , kinase , in vitro , organic chemistry , catalysis , polymer
Abstract A synthetic protocol has been designed to synthesize grecoketidone ( 2k ), 5‐hydroxylapachol ( 2g ), and the recently discovered natural products juglonbutin ( 2o ) and its derivatives, leading to a small library of different 1,4‐naphthoquinones with the intention of finding new active compounds. Within our collection, 2‐ O ‐alkylated naphthoquinones with an ester functionality in the side‐chain and a free OH group at C‐5 showed the best activities. Compounds 2f , 2m , and 2n showed GI 50 values against 12 tumor cell lines in the lower micromolar range and juglonbutin ( 2o ) showed remarkably efficient inhibition of the glycogen synthase kinase 3β with an IC 50 value of 2.03 μ M . Furthermore, studies on the mode of action of the most active cytotoxic compounds have been carried out. To the best of our knowledge, this is the first report on the synthesis of juglonbutin ( 2o ) and its biological activity.