title: Discovery of novel andrographolide derivatives as cytotoxic agents.
abstract: The natural diterpenoid andrographolide (1) exhibits various biological activities. Seventeen derivatives of 1 were prepared via esterification and etherification of 14-dehydroxy-11,12-didehydroandrographolide (2). Most derivatives demonstrated significant inhibition against tumor cell growth. The most active compounds, 3b and 3c, had GI50 values of 1.46-9.19 μM against A549, DU145, KB and KB-Vin tumor cells. In an immunocytochemical study, treatment with compound 3c disrupted microtubule dynamics in PC-3 cells, but caused no accumulation of metaphase cells, which is a phenotype dissimilar from that of 1. This difference suggests that structural modification of 1 resulted in a shift in the underlying molecular mechanism.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Shanfu
authors.initials: S
authors.lastname: Wei
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Tang
authors.forename: Huiming
authors.initials: H
authors.lastname: Hua
authors.forename: Emika
authors.initials: E
authors.lastname: Ohkoshi
authors.forename: Masuo
authors.initials: M
authors.lastname: Goto
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Wang
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C030419:andrographolide