title: Synthesis and biological evaluation of glaucocalyxin A derivatives as potential anticancer agents.
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.
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Chengwen
authors.initials: C
authors.lastname: Xue
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Electronic address: qiaochunhua@suda.edu.cn.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Qiao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007624:KB Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; C055124:glaucocalyxin A
keywords: Antitumor; Glaucocalyxin A; Glaucocalyxin A derivatives; Prodrug; Structure activity relationship