Synthesis of unsymmetrical biphenyls as potent cytotoxic agents

  • Bioorg Med Chem Lett. 2008 Oct 1;18(19):5272-6. doi: 10.1016/j.bmcl.2008.08.050.
Gang Wu  1 ,  Huan-Fang Guo ,  Kun Gao ,  Yi-Nan Liu ,  Kenneth F Bastow ,  Susan L Morris-Natschke ,  Kuo-Hsiung Lee ,  Lan Xie
Affiliations
  • 1. Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
PMID: 18782668 DOI: 10.1016/j.bmcl.2008.08.050
Abstract

Twenty-six unsymmetrical biphenyls were synthesized and evaluated for cytotoxic activity against DU145, A549, KB and KB-Vin tumor cell lines. Three compounds 27, 35 and 40 showed very potent activity against the HTCL panel with an IC(50) value range of 0.04-3.23 microM. In addition, fourteen active compounds were all more potent against the drug-resistant KB-Vin cell line than the parental KB cell line. Preliminary SAR analysis indicated that two bulky substituents on the 2,2'-positions of unsymmetrical biphenyl skeleton are necessary and crucial for in vitro Anticancer activity, thus providing a good starting point to develop unsymmetrical biphenyls as novel Anticancer agents.