Synthesis and Cytotoxic Activity of a Small Naphthoquinone Library: First Synthesis of Juglonbutin1. Issue 24 (15th July 2014)

• Record Type: Journal Article
• Authors: Brötz, Elke; Herrmann, Jennifer; Wiese, Jutta; Zinecker, Heidi; Maier, Armin; Kelter, Gerhardt; Imhoff, Johannes F.; Müller, Rolf; Paululat, Thomas
• Is Part Of: European journal of organic chemistry. Issue 24(2014)
• Page Start: 5318
• Page End: 5330
• Publication Date: 2014-07-15
• Subjects: Natural products -- Quinones -- Medicinal chemistry -- Toxicity -- Antitumor agents; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402272
• Languages: English
• ISSNs: 1434-193X

Abstract

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. Compounds2f, 2m, and2n showed GI50 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 IC50 value of 2.03 μM . 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. Abstract : A synthetic protocol has been designed to synthesize a small naphthoquinone library based around the natural products grecoketidone, hydroxylapachol, and juglonbutin. Biological profiling on some of the synthesized naphthoquinones revealed good activities against different tumor cell lines, with juglonbutin showing a remarkable activity against GSK3β with an IC50 value of 2 μM .