Synthesis, selective cytotoxicities and probable mechanism of action of 7-methoxy-3-arylflavone-8-acetic acids

  • Bioorg Med Chem. 2014 Mar 1;22(5):1539-47. doi: 10.1016/j.bmc.2014.01.042.
Zhong-Zhen Zhou  1 ,  Chun-Ping Gu  1 ,  Yan-Hong Deng  1 ,  Guang-Hua Yan  1 ,  Xiao-Fang Li  2 ,  Le Yu  1 ,  Wen-Hua Chen  3 ,  Shu-Wen Liu  4
Affiliations
  • 1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
  • 2. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
  • 3. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
  • 4. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
PMID: 24518295 DOI: 10.1016/j.bmc.2014.01.042
Abstract

Thirteen new analogues of flavone-8-acetic acid, that is, compounds 10a-m bearing a methoxy group at the 7-position and diverse subsitiuents on the benzene ring at the 2- and 3-positions of flavone nucleus, were synthesized and evaluated for their direct antiproliferative effects on two human tumor cell lines and for their indirect antiproliferative activities in the transwell co-culture system. The results indicated that most of compounds 10a-m showed moderate direct cytotoxicities. Among them, compound 10i exhibited higher direct cytotoxicity and selectivity for both cell lines over BJ human foreskin fibroblast cells than 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Interestingly, compared with DMXAA, compound 10e showed comparable indirect cytotoxicity and higher selectivity. In addition, compound 10e was found to be able to induce tumor necrosis factor α (TNF-α) production in human peripheral blood mononuclear cells.

Keywords
3-Arylflavone-8-acetic acid; Direct cytotoxicity; Indirect cytotoxicity; Transwell co-culture system; Tumor necrosis factor α.