title: Cytotoxic activity of the alkaloids from Broussonetia papyrifera fruits.
abstract: BACKGROUND
  Broussonetia papyrifera (L.) Vent. (Moraceae), a traditional Chinese medicinal herb, has been extensively applied for many years to treat various diseases. Recently, a number of compounds with biological and pharmacological activities have been extracted from the plant and used as chemotherapeutic candidates to treat a range of diseases such as cancer.
  
  
  OBJECTIVE
  The current study was designed to isolate the alkaloid compounds from ethyl acetate extraction of Broussonetia papyrifera fruits, and to evaluate the cytotoxic activity of total alkaloids as well as individual isoquinoline alkaloids from B. papyrifera fruits.
  
  
  METHODS
  Alkaloid compounds were isolated from the ethyl acetate extraction by silica gel column chromatography methods using CHCl3/MeOH as eluents. The compounds' structures were determined by detailed analysis of NMR, MS spectral data, and chemical methodology. Cytotoxic activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods against human A375, Hela, BEL-7402 cancer cells, and non-cancer cells.
  
  
  RESULTS
  Two isoquinonline alkaloids were isolated and characterized as N-norchelerythrine and dihydrosanguinarine. The total alkaloids and seven individual alkaloids had higher activities on BEL-7402 and Hela cell lines with low IC50 values 6.61-47.41 and 5.97-40.17 μg/mL (<50 μg/mL). Nitidine, broussonpapyrine, and chelerythrine had strong toxic on non-cancer cells with IC50 value 18.01, 19.91, and 22.31 μg/mL, respectively.
  
  
  CONCLUSIONS
  N-Norchelerythrine and dihydrosanguinarine were isolated from this plant for the first time. Our data implicated that seven isoquinoline alkaloids had cytotoxity with structure-activity relationships, which provided fundamental information for further modification of their anticancer effect.
authors.affiliation: School of Biomedical Sciences, Huaqiao University , Quanzhou , China and.
authors.forename: Su-Qiu
authors.initials: SQ
authors.lastname: Pang
authors.forename: Guo-Quan
authors.initials: GQ
authors.lastname: Wang
authors.forename: Jun-sheng
authors.initials: JS
authors.lastname: Lin
authors.forename: Yong
authors.initials: Y
authors.lastname: Diao
authors.forename: Rui-an
authors.initials: RA
authors.lastname: Xu
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031623:Broussonetia; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D006367:HeLa Cells; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*
chemical_list: D000470:Alkaloids; D003603:Cytotoxins; D010936:Plant Extracts
keywords: Anticancer effect; isoquinoline alkaloids; structure–activity relationship