title: In vitro cytotoxic activity of novel protoflavone analogs - selectivity towards a multidrug resistant cancer cell line.
abstract: BACKGROUND
  Protoapigenone (PA), a natural flavonoid possessing an unusual p-quinol moiety on its B ring, is a prospective novel lead compound against cancer currently in development, together with WYC0209, a potent synthetic PA analog. Structure activity relationships (SAR) concerning different 1'-O-alkyl side-chains were also studied on two sets of derivatives.
  
  
  METHODS
  Fifteen 1'-O-alkyl protoflavone derivatives were synthesized from genkwanin or 4'-hydroxy-6-methylflavone, thirteen of which are new compounds. All compounds were tested for their cytotoxic effect on four human cancer cell lines, such as HepG2 and Hep3B (hepatic), A549 (lung) and MDA-MB-231 (breast) cell lines, with doxorubicin as a positive control. All compounds, as well as PA, WYC0209 and fourteen of their previously reported analogs were also tested on a multidrug-resistant (MDR) sub-cell line of L5178 mouse T-cell lymphoma and on its parental counterpart (PAR).
  
  
  RESULTS
  In general, derivatives bearing a free hydroxyl group at C-1' exerted the strongest activities, while C-1'-substituted compounds were found to be much weaker. Derivatives of 6-methylflavone exhibited mild, but statistically significant selectivity towards the MDR cell line.
  
  
  CONCLUSIONS
  The results are in agreement with our previous findings for fundamental SAR of protoflavones. 6-Methylated protoflavones may serve as valuable leads for developing selective compounds against MDR cancer. Identical activity of other derivatives on the PAR and MDR cell lines suggests that cancer cells cannot exhibit resistance to protoflavones by ABCB1 efflux pump overexpression.
authors: Institute of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors: B
authors: B
authors: Danko
authors: A
authors: A
authors: Martins
authors: D W
authors: DW
authors: Chuang
authors: H C
authors: HC
authors: Wang
authors: L
authors: L
authors: Amaral
authors: J
authors: J
authors: Molnár
authors: F R
authors: FR
authors: Chang
authors: Y C
authors: YC
authors: Wu
authors: A
authors: A
authors: Hunyadi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007940:Leukemia L5178 / Q000188:drug therapy; D051379:Mice; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047309:Flavones