title: Development of novel conformation-constrained cytotoxic derivatives of cheliensisin A by embedment of small heterocycles.
abstract: Cheliensisin A is a natural styryl-lactone isolated from Goniothalamus cheliensis Hu in considerably large quantity with putative anticancer activities. However, its poor water solubility and chemical instability have precluded cheliensisin A as a potential drug candidate. To explore the strategy to overcome these problems, 21 novel derivatives of cheliensisin A with different substitutions at C-7 and C-8 positions were designed and synthesized. Inhibition of proliferation against five tumors cell lines indicates that eight new derivatives with embedment of oxazole or oxazoline exhibit improved cytotoxicity on SK-BR-3 and PANC-1, and compounds 2d and 2g show 5-8 folds higher potency than cisplatin. HPLC investigation of representative compounds indicates that oxazole and oxazoline analogs exhibit much improved chemical stability than their natural parent.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Deng
authors.forename: Jia
authors.initials: J
authors.lastname: Su
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhu-Jun
authors.initials: ZJ
authors.lastname: Yao
authors.forename: Qin-Shi
authors.initials: QS
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D006571:Heterocyclic Compounds; D011753:Pyrones; C504861:cheliensisin A