Synthesis, biological evaluation and SAR analysis of O-alkylated analogs of quercetin for anticancer

  • Bioorg Med Chem Lett. 2014 Sep 15;24(18):4424-4427. doi: 10.1016/j.bmcl.2014.08.006.
Zhi-Hao Shi  1 ,  Nian-Guang Li  2 ,  Yu-Ping Tang  3 ,  Qian-Ping Shi  4 ,  Wei Zhang  4 ,  Peng-Xuan Zhang  4 ,  Ze-Xi Dong  4 ,  Wei Li  4 ,  Xu Zhang  4 ,  Hai-An Fu  5 ,  Jin-Ao Duan  6
Affiliations
  • 1. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Department of Organic Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
  • 2. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. Electronic address: [email protected].
  • 3. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. Electronic address: [email protected].
  • 4. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
  • 5. Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, United States.
  • 6. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. Electronic address: [email protected].
PMID: 25139569 DOI: 10.1016/j.bmcl.2014.08.006
Abstract

O-Alkylated quercetin analogs were synthesized and their Anticancer activities were assessed by a high-throughout screening (HTS) method. The structure-activity relationships (SAR) showed that introduction of long alkyl chain such as propyl group at the C-3 OH position or short alkyl chain such as ethyl group at the C-4' OH position were very important for keeping inhibitory activities against the 16 Cancer cell lines. Furthermore, when the two n-butyl groups were introduced into the C-3, C-7 or C-4', C-7 positions, the Anticancer activity was enhanced.

Keywords
Alkylation; Anticancer; Quercetin; Structure–activity relationship.