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.
- 1. College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
- 2. College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: [email protected].
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.