title: Antiproliferative effect of alkaloids via cell cycle arrest from Pseuduvaria rugosa.
abstract: BACKGROUND
  Pseuduvaria rugosa (Blume) Merr. (Annonacaea) grows widely in the south and southeast regions of Thailand. Preliminary screening for biological activities revealed that crude hexane, ethyl acetate, and acetone extracts from mixtures of leaves and twigs of P. rugosa showed cytotoxicity.
  
  
  OBJECTIVE
  Chemical constituents and their antiproliferative activity in K562, U937, and HL-60 human leukemic cell lines from P. rugosa were performed for the first time.
  
  
  METHODS
  The isolated compounds were obtained from chromatographic separation. The structures were established by spectroscopic techniques including IR, UV, NMR together with 2D NMR (HMBC, COSY, and NOE) and MS. The K562, U937, and HL-60 cell lines were treated with isolated aporphine alkaloids (0-100 µg/mL) and cell viability was measured with the MTT assay. Cell cycle analysis was performed using propidium iodide (PI) based staining methods.
  
  
  RESULTS
  Two known aporphine alkaloids, 1,2,3-trimethoxy-5-oxonoraporphine (1) and ouregidione (2) were isolated. Treatment of the cells with compounds 1 and 2 at a concentration of 100 µg/mL for 72 h reduced the viability of K562, U937, and HL-60 cell lines to 63 and 64, 38 and 66, and 49 and 64%, respectively. In addition, compounds 1 and 2, at a concentration of 100 µg/mL, exposed to U937 and HL-60 cell lines showed cell cycle arrest. The U937 cell line treated with compounds 1 and 2 increased significantly the proportion of the cell in S phase, whereas the HL-60 cell line-induced G2/M and G1 phase, respectively.
  
  
  CONCLUSIONS
  The results showed that 1,2,3-trimethoxy-5-oxonoraporphine and ouregidione-induced cytotoxicity with HL-60, U937, and K562 cells where 1,2,3-trimethoxy-5-oxonoraporphine was more active than ouregidione.
authors: Laboratory of Natural Products, Faculty of Science and Center for Innovation in Chemistry, Lampang Rajabhat University, Lampang, Thailand.
authors: Orathai
authors: O
authors: Uadkla
authors: Supachai
authors: S
authors: Yodkeeree
authors: Mongkol
authors: M
authors: Buayairaksa
authors: Puttinan
authors: P
authors: Meepowpan
authors: Narong
authors: N
authors: Nuntasaen
authors: Pornngarm
authors: P
authors: Limtrakul
authors: Wilart
authors: W
authors: Pompimon
mesh_terms: D029061:Annonaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001060:Aporphines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D011166:Porphyrins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry; D013785:Thailand
chemical_list: C400348:1,2,3-trimethoxy-5-oxonoraporphine; D000972:Antineoplastic Agents, Phytogenic; D001060:Aporphines; D010936:Plant Extracts; D011166:Porphyrins; D012997:Solvents; C582597:ouregidione