title: New method for recognition of sterol signalling molecules: methinium salts as receptors for sulphated steroids.
abstract: In this work, we studied indolium and benzothiazolium pentamethine salts 1-3 as novel type of receptors for the recognition of sulphated signalling molecules (sulphated steroids: oestrone, pregnenolone and cholesterol sulphate). A recognition study was performed in an aqueous medium (1mM phosphate buffer (H2O:MeOH; 99:1 (v/v))) at pH 7.34. The tested salts displayed a high affinity for these sulphated analytes, mainly for cholesterol sulphate. However, no interaction between the salts and control, non-sulphated sterol analytes (cholesterol and bile acid) was observed. The highest affinity for the sulphated steroids was observed for benzothiazole salt 1. This salt also displayed different spectral behaviour from that observed for carbocyanine salts 2 and 3. In this presence of cholesterol sulphate, benzothiazole salt 1 displayed significant spectral changes depending on the medium used: a blue shift in the aqueous medium and a red shift in the methanolic one (H2O:MeOH; 2:1 (v/v)). Subsequently preliminary in vivo study showed that, salt 1 significantly inhibits a growth of breast carcinoma on Nu/nu mice model.
authors.affiliation: Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic; First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Kejík
authors.affiliation: Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic; First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Bříza
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Králová
authors.affiliation: First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Mikula
authors.affiliation: First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Poučková
authors.affiliation: First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Martásek
authors.affiliation: Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic; Zentiva Development (part of Sanofi Generic group), U Kabelovny 130, 102 37 Prague 10, Czech Republic. Electronic address: vladimir.kral@vscht.cz.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Král
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy; D002232:Carbocyanines / Q000737:chemistry; D002788:Cholesterol Esters / Q000737:chemistry* / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D008819:Mice, Nude; D011284:Pregnenolone / Q000737:chemistry* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D002232:Carbocyanines; D002788:Cholesterol Esters; D006571:Heterocyclic Compounds; D004970:Estrone; D011284:Pregnenolone; C005465:benzothiazole; C007045:cholesteryl sulfate; C017296:estrone sulfate
keywords: Molecular recognition; Polymethinium salts; Sulphated sterols; Synthetic receptors