2. Academic Validation
  3. Synthesis and biological evaluation of glaucocalyxin A derivatives as potential anticancer agents

Synthesis and biological evaluation of glaucocalyxin A derivatives as potential anticancer agents

  • Eur J Med Chem. 2014 Oct 30:86:235-41. doi: 10.1016/j.ejmech.2014.08.061.
Jing Yang 1,  Yanli Liu 1,  Chengwen Xue 1,  Wei Yu 1,  Jian Zhang 1,  Chunhua Qiao 2
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
  • 2 College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: qiaochunhua@suda.edu.cn.
PMID: 25164762 DOI: 10.1016/j.ejmech.2014.08.061
Abstract

A series of Mannich base type derivatives of Glaucocalyxin A (GLA) were designed and prepared. The cytotoxicity of these compounds was evaluated against six tumor cell lines (SMMC-7721, B16, SGC-7901, A549, KB, HL-60). Most compounds exhibited potent antiproliferative effects with low micromolar IC50 values. Compound 1 with para methyl benzyl amine moiety and compound 16 with cyclohexylamine moiety displayed the highest inhibition efficacy. Significantly, the cytotoxicity of compound 1 was much lower than GLA against the normal human liver cell (HL-7702). The in vitro stability assay revealed that transformation of GLA to Mannich base type derivatives improved the compound stability in rat plasma. Finally, decomposition product analysis supported that compound 1 could act as a prodrug and release GLA in the intracellular environment.

Keywords

Antitumor; Glaucocalyxin A; Glaucocalyxin A derivatives; Prodrug; Structure activity relationship.

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