title: Synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents.
abstract: To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the "combination principle" in drug discovery. The ligustrazine derivatives' anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 α,12 α-dihydroxy-5β-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD₅₀ value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China.
authors.forename: Penglong
authors.initials: P
authors.lastname: Wang
authors.forename: Gaimei
authors.initials: G
authors.lastname: She
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Honggui
authors.initials: H
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Yinqiu
authors.initials: Y
authors.lastname: Cao
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Haimin
authors.initials: H
authors.lastname: Lei
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000187:drug effects; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D011719:Pyrazines; C017953:tetramethylpyrazine