title: Eaton's reagent-mediated domino π-cationic arylations of aromatic carboxylic acids to Iasi-red polymethoxylated polycyclic aromatic hydrocarbons: products with unprecedented biological activities as tubulin polymerization inhibitors.
abstract: A rapid domino π-cationic arylation of aromatic carboxylic acids, mediated by Eaton's reagent, has been developed for the synthesis of Iasi-red polymethoxylated polycyclic aromatic hydrocarbons (PAHs). This route is currently the easiest method to obtain such popular PAH compounds, which bear in addition numerous methoxy groups. The domino process was generalized, the structure of the obtained red products and the mechanism of their formations were elucidated, and some of their photophysical properties were determined. Newly synthesized polymethoxylated-PAHs were tested for their interaction with tubulin polymerization as well as for their cytotoxicity on a panel of NCI-60 human cancer cell lines. Interestingly, one of these rubicene derivatives exhibited remarkable cytotoxicity in vitro, including inhibition of leukemia, colon, melanoma, CNS, and ovarian cancer cell lines with GI50 values in the low nanomolar range (GI50 < 10 nM).
authors.affiliation: Univ Lille Nord de France, 59000 Lille (France); UCLille, EA 4481 (GRIIOT), Laboratoire de Pharmacochimie, HEI, 13 rue de Toul, F-59046 Lille (France); Department of Organic Chemistry, 'Al. I. Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi (Romania). Alina.GHINET@hei.fr.
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautret
authors.forename: Nathalie Van
authors.initials: NV
authors.lastname: Hijfte
authors.forename: Bertrand
authors.initials: B
authors.lastname: Ledé
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hénichart
authors.forename: Elena
authors.initials: E
authors.lastname: Bîcu
authors.forename: Ulrich
authors.initials: U
authors.lastname: Darbost
authors.forename: Benoît
authors.initials: B
authors.lastname: Rigo
authors.forename: Adam
authors.initials: A
authors.lastname: Daïch
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D058105:Polymerization / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D007202:Indicators and Reagents; D011084:Polycyclic Aromatic Hydrocarbons; D014404:Tubulin; D050257:Tubulin Modulators
keywords: antitumor agents; conjugation; domino reactions; dyes/pigments; polycycles