title: Mono- or di-fluorinated analogues of flavone-8-acetic acid: synthesis and in vitro biological activity.
abstract: BACKGROUND
  Previously, the antitumour activity of some flavone-8-acetic acid (FAA) derivatives substituted with an acid function in position 2 of the benzene ring was evaluated. The most active compound resulted the one bearing a fluorine atom in position 7 of the flavone nucleus. In this paper, we evaluated new mono- or di-fluorinated FAA derivatives.
  
  
  METHODS
  The cytotoxicity towards two human ovarian adenocarcinoma cell lines, the capability to stimulate human mononuclear cells and murine macrophages' lytic properties were evaluated by MTT. Moreover, the potentiation of lipopolysaccharide (LPS) activity was studied by ELISA analysis of TNF-alpha release.
  
  
  RESULTS
  The analogues showed a direct cytotoxicity comparable to that of 5,6-dimethyl-xanthen-9-one-4-acetic acid (DMXAA), at present in clinical trials. None of the tested compounds was able to stimulate human mononuclear cells' lytic properties after either 4- or 24-h treatment, while after 4-h treatment, the derivative 5a was more able to stimulate murine macrophages with respect to DMXAA. Moreover, a significant increase of 5c and 5d activation was obtained with LPS association, reflected by TNF-alpha production as well.
  
  
  CONCLUSIONS
  Like FAA, the new fluorinated derivatives 5a, 5c and 5d showed remarkable activity in murine cells, but this was not confirmed in human models.
authors.affiliation: Department of Pharmacology and Anaesthesiology, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy. maria.carrara@unipd.it
authors.forename: Maria
authors.initials: M
authors.lastname: Carrara
authors.forename: Antonella
authors.initials: A
authors.lastname: Zampiron
authors.forename: Mariagnese
authors.initials: M
authors.lastname: Barbera
authors.forename: Anna
authors.initials: A
authors.lastname: Caputo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisi
authors.forename: Silvia
authors.initials: S
authors.lastname: Gobbi
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.forename: Lorna
authors.initials: L
authors.lastname: Piazzi
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
authors.forename: Piero
authors.initials: P
authors.lastname: Valenti
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D006845:Hydrocarbons, Fluorinated; D014409:Tumor Necrosis Factor-alpha; C049328:flavone acetic acid