2. Academic Validation
  3. Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents

Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents

  • Bioorg Med Chem. 2014 Jan 1;22(1):374-80. doi: 10.1016/j.bmc.2013.11.013.
Yong Ling 1,  Zhiqiang Wang 1,  Hongyan Zhu 2,  Xuemin Wang 2,  Wei Zhang 2,  Xinyang Wang 2,  Li Chen 3,  Zhangjian Huang 4,  Yihua Zhang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Medical College, Nantong University, Nantong 226001, PR China.
  • 2 Medical College, Nantong University, Nantong 226001, PR China.
  • 3 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
  • 4 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China.
  • 5 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: zyhtgd@hotmail.com.
PMID: 24300920 DOI: 10.1016/j.bmc.2013.11.013
Abstract

Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were synthesized and biologically evaluated. It was found that FTS-monoamide molecules (10a-g) displayed strong anti-proliferative activity against seven human Cancer cell lines, superior to FTS and FTS-bisamide compounds (11a-g). The mono-amide 10f was the most active, with IC₅₀s of 3.78-7.63 μM against all tested Cancer cells, even more potent than sorafenib (9.12-22.9 μM). In addition, 10f induced SMMC-7721 cell Apoptosis, down-regulated the expression of Bcl-2 and up-regulated Bax and Caspase-3. Furthermore, 10f had the improved aqueous solubility relative to FTS. Finally, treatment with 10f dose-dependently inhibited the Ras-related signaling pathways in SMMC-7721 cells. Collectively, 10f could be a promising candidate for the intervention of human cancers.

Keywords

Anti-cancer agents; Cell apoptosis; Diamines; Farnesylthiosalicylic acid; Ras-related signaling pathway.

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