%0 Journal Article
%T Direct Semi-Synthesis of the Anticancer Lead-Drug Protoapigenone from Apigenin, and Synthesis of Further New Cytotoxic Protoflavone Derivatives
%A Attila Hunyadi
%A Da-Wei Chuang
%A Balazs Danko
%A Michael Y. Chiang
%A Chia-Lin Lee
%A Hui-Chun Wang
%A Chin-Chung Wu
%A Fang-Rong Chang
%A Yang-Chang Wu
%J PLOS ONE
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0023922
%X Protoapigenone, a natural flavonoid possessing an unusual p-quinol moiety on its B-ring, is a novel prospective anticancer agent with low toxicity that is currently in development. The first economical, one-step synthesis of protoapigenone from apigenin is described on up to gram scale. 13 new 1¡ä-O-alkylflavone analogs were also synthesized, either from apigenin or ¦Â-naphthoflavone. The in vitro cytotoxic activity of each compound was tested on six human cancer cell lines (HepG2, Hep3B, Ca9-22, A549, MCF-7 and MDA-MB-231). In the case of 1¡ä-O-alkyl-protoapigenone derivatives, structure-activity relationships were found depending on the side-chain, and protoapigenone 1¡ä-O-butyl ether was found to exert significantly stronger activity against three of the cell lines (Hep3B, MCF-7 and MDA-MB-231) than its non-substituted analog, protoapigenone itself. In contrast to this, all ¦Â-naphthoflavone derivatives bearing the same pharmacophore on their B-ring showed decreased cytotoxic activities when substituted with an O-alkyl side-chain at position 1¡ä, comparing to that of the non-substituted compound.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023922