title: Towards new boron carriers for boron neutron capture therapy: metallacarboranes and their nucleoside conjugates.
abstract: Thymidine conjugates containing metallacarborane, {8-[5-(N(3)-thymidine)-3-oxa-pentoxy]-3-cobalt bis(1,2-dicarbollide)}- (5) and {8-[5-(O(4)-thymidine)-3-oxa-pentoxy]-3-cobalt bis(1,2-dicarbollide)}- (6) ions and several simple [3-cobalt bis(1,2-dicarbollide)]- ion (1) derivatives have been studied as potential boron carriers for BNCT. Compound 6 and some nonnucleoside derivatives of 1 were not toxic above 100 microM. The partition coefficient for both metallacarborane bearing thymidine conjugates 5 and 6 was more than 500 times higher than that of unmodified nucleoside. The cellular uptake studies showed accumulation of compounds 6 in V79 Chinese hamster cells but not of compound 5. The low toxicity of conjugate type of 6 together with its high partition coefficient suggest that judicially designed derivatives of metallacarboranes can be considered as potential boron carriers for BNCT.
authors.affiliation: Center of Medical Biology, Laboratory of Molecular Virology and Biological Chemistry, Polish Academy of Sciences, 106 Lodowa Street, Lodz 93-232, Poland.
authors.forename: Zbigniew J
authors.initials: ZJ
authors.lastname: Leśnikowski
authors.forename: Edyta
authors.initials: E
authors.lastname: Paradowska
authors.forename: Agnieszka B
authors.initials: AB
authors.lastname: Olejniczak
authors.forename: Mirosława
authors.initials: M
authors.lastname: Studzińska
authors.forename: Petra
authors.initials: P
authors.lastname: Seekamp
authors.forename: Uw
authors.initials: U
authors.lastname: Schüssler
authors.forename: Detlef
authors.initials: D
authors.lastname: Gabel
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.forename: Jaromir
authors.initials: J
authors.lastname: Plesek
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy; D002470:Cell Survival / Q000187:drug effects*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D013936:Thymidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014709:Vero Cells
chemical_list: D001896:Boron Compounds; D013936:Thymidine