title: A spectroscopic study of substituted anthranilic acids as sensitive environmental probes for detecting cancer cells.
abstract: Small-molecule fluorescent reporters of disease states are highly sought after, yet they remain elusive. Anthranilic acids are extremely sensitive environmental probes, and hold promise as general but selective agents for cancer-cell detection if they can be equipped with the appropriate targeting groups. The optical properties of a small library of N-isopropyl invariant anthranilic acids were investigated in methanol and chloroform. Points of variation included: fluoro, trifluoromethyl, or cyano substitution on the aromatic ring, and derivitization of the parent carboxylic acid as esters or secondary carboxamides. Phenylboronic acid conjugation at the carboxylic acid alongside un-, mono-, and dimethylated 2-amino groups was also explored. The boron-containing anthranilic acids were also evaluated as sensitive fluorescent probes for cancer cells using laser scanning confocal microscopy. In general, the compounds produced blue fluorescence that was strongly influenced by substitution and environment. 4-Trifluoromethyl and 4-cyano esters proved to be the most sensitive environmental probes with quantum yields as large as 100% in chloroform, and enhancements of up to 30-fold on going from methanol to chloroform. Stokes shifts ranged from 63 to 120nm, generally increasing with ortho-substitution and environmental polarity. It was demonstrated that phenylboronic acid conjugation was an attractive method for cancer cell detection via boronate ester formation with overexpressed glycoproteins (with no interference from normal, healthy cells), presumably due to favorable boron-sialic acid interactions.
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick E1C 8X3, Canada. Electronic address: aculf@sussex-research.com.
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Culf
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Huimin
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, Nova Scotia B4P 2R6, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Monro
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick E1C 8X3, Canada.
authors.forename: Anirban
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick E1C 8X3, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Barnett
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick E1C 8X3, Canada.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Ouellette
authors.affiliation: National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Čuperlović-Culf
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, Nova Scotia B4P 2R6, Canada. Electronic address: sherri.mcfarland@acadiau.ca.
authors.forename: Sherri A
authors.initials: SA
authors.lastname: McFarland
mesh_terms: D001897:Boronic Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000175:diagnosis*; D062367:ortho-Aminobenzoates / Q000737:chemistry*
chemical_list: D001897:Boronic Acids; D005456:Fluorescent Dyes; D062367:ortho-Aminobenzoates; C010686:benzeneboronic acid
keywords: Anthranilic acids; Biological probes; Boronic acids; Cancer cell detection; Fluorescent probes