Synthesis and anticancer potential of novel xanthone derivatives with 3,6-substituted chains

  • Bioorg Med Chem. 2016 Sep 15;24(18):4263-4271. doi: 10.1016/j.bmc.2016.07.020.
Chaomei Liu  1 ,  Mei Zhang  2 ,  Zhenhuan Zhang  2 ,  Steven B Zhang  2 ,  Shanmin Yang  2 ,  Amy Zhang  2 ,  Liangjie Yin  2 ,  Steven Swarts  2 ,  Sadasivan Vidyasagar  2 ,  Lurong Zhang  2 ,  Paul Okunieff  2
Affiliations
  • 1. Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA. Electronic address: [email protected].
  • 2. Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
PMID: 27448774 DOI: 10.1016/j.bmc.2016.07.020
Abstract

In an effort to develop new drug candidates with enhanced Anticancer activity, our team synthesized and assessed the cytotoxicity of a series of novel xanthone derivatives with two longer 3,6-disubstituted amine carbonyl methoxy side chains on either benzene ring in selected human Cancer cell lines. An MTT assay revealed that a set of compounds with lower IC50 values than the positive control, 5-FU, exhibited greater Anticancer effects. The most potent derivative (XD8) exhibited Anticancer activity in MDA-MB-231, PC-3, A549, AsPC-1, and HCT116 cells lines with IC50 values of 8.06, 6.18, 4.59, 4.76, and 6.09μM, respectively. Cell cycle analysis and Apoptosis activation suggested that the mechanism of action of these derivatives includes cell cycle regulation and Apoptosis induction.

Keywords
3,6-Substituted long chains; A549; Anticancer potential; Apoptosis; Caspase 3/7 activity; Cell cycle arrest; IC(50); Structure–activity relationship; Synthesis; Xanthone derivatives.
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