Anti-tumoral activities of dioncoquinones B and C and related naphthoquinones gained from total synthesis or isolation from plants.
Dioncoquinones belong to a family of natural naphthoquinone products of interest due to their promising anti-tumoral and anti-infective activities. In particular, dioncoquinones A (5) and B (6) have been shown to be highly active against Leishmania major and multiple myeloma cells without any significant toxicity toward normal blood cells. Their effective concentrations against multiple myeloma cell lines were similar to those of melphalan, a well known DNA-alkylating agent used in a standard therapy against B cell lymphoma and multiple myeloma. We report on the first total synthesis of the highly oxygenated anti-tumoral agent dioncoquinone B (6) and the isolation of its new, even higher-oxygenated analogs, dioncoquinones C (7), D (8), and E (9), from cell cultures of Triphyophyllum peltatum. In addition, several derivatives of these compounds were synthesized, including dioncoquinone C (7), and a small library of naphthoquinones was created. Furthermore, the first structure-activity relationship (SAR) study on this class of compounds was conducted, showing that each of the three hydroxy groups, at C-3, C-5, and C-6, is required for improved anti-tumoral activities and decreased cytotoxicities.
Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
Gerhard
G
Bringmann
Guoliang
G
Zhang
Anastasia
A
Hager
Michael
M
Moos
Andreas
A
Irmer
Ralf
R
Bargou
Manik
M
Chatterjee
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D045603:Dioncophyllaceae / Q000737:chemistry*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009285:Naphthoquinones