Synthesis and In Vitro Anticancer Evaluation of Novel Chrysin and 7-Aminochrysin Derivatives
Szabolcs Mayer,
Péter Keglevich,
Péter Ábrányi-Balogh,
Áron Szigetvári,
Miklós Dékány,
Csaba Szántay,
László Hazai
Affiliations
Szabolcs Mayer
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Gellért tér 4, H-1111 Budapest, Hungary
Péter Keglevich
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Gellért tér 4, H-1111 Budapest, Hungary
Péter Ábrányi-Balogh
Medicinal Chemistry Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar tudósok krt. 2, H-1117 Budapest, Hungary
Áron Szigetvári
Spectroscopic Research Department, Gedeon Richter Plc., P.O. Box 27, H-1475 Budapest, Hungary
Miklós Dékány
Spectroscopic Research Department, Gedeon Richter Plc., P.O. Box 27, H-1475 Budapest, Hungary
Csaba Szántay
Spectroscopic Research Department, Gedeon Richter Plc., P.O. Box 27, H-1475 Budapest, Hungary
László Hazai
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Gellért tér 4, H-1111 Budapest, Hungary
Chrysin is a naturally occurring flavonoid with mild anticancer activity. In this paper we report the synthesis of new chrysin derivatives alkylated with N-phenylchloroacetamides in position 7. A novel method was developed for the preparation of 7-aminochrysin derivatives via the Smiles rearrangement, resulting in diphenylamine-type compounds. In silico studies of the Smiles rearrangement were performed. We also present the in vitro antiproliferative activity of the synthesized compounds against 60 human tumor cell lines (NCI60). The most potent derivative exhibited nanomolar antitumor activity on the MCF7 cell line of breast cancer (GI50 = 30 nM) and on the HCT-15 cell line of colon cancer (GI50 = 60 nM).
