Počet záznamů: 1  

Synthesis of selectively deuterated and tritiated lupane derivatives with cytotoxic activity

  1. 1. 0398914 - UOCHB-X 2014 RIV HU eng J - Článek v odborném periodiku
    Vlk, M. - Urban, M. - Elbert, Tomáš - Šarek, J.
    Synthesis of selectively deuterated and tritiated lupane derivatives with cytotoxic activity.
    Journal of Radioanalytical and Nuclear Chemistry. Roč. 298, č. 2 (2013), s. 1149-1157 ISSN 0236-5731
    Grant ostatní:GA ČR(CZ) GA305/09/1216
    Institucionální podpora: RVO:61388963
    Klíčová slova: isotopic labelling * tritium * deuterium * betulin * betulinic acid * cytotoxicity
    Kód oboru RIV: CB - Analytická chemie, separace
    Impakt faktor: 1.415, rok: 2013

    The aim of this work was to synthesize deuterated and tritiated analogues of highly oxidized lupane derivatives known from our group. We selected compounds that previously showed very high cytotoxic activity on multiple cancer cell lines in order to further investigate the mechanism of their action. From starting material (compounds 1-4), we obtained benzyl platanate (5) and its reaction with deuteromethyltriphenylphosphonium iodide gave deuterated compound 6. Following benzyl deprotection gave free acid 7 and oxidation with SeO2 gave 30-oxo-[29-H-2(2)]lup-20(29)-en-28-oic acid (8), which is one of the most active compounds synthesized in our group to date (IC50 6 mu mol/L on CEM cell line). The alkylation of benzyl 2-hydroxy-3-oxolupa-1,20(29)-dien-28-oate (9) with methyliodide or deuteromethyliodide followed by a series of deprotection and hydrogenation steps gave compounds 10-14, where 2 beta-[31-H-2(3)]methoxy-3-oxolupan-20(29)-en-28-oic acid (13) is especially interesting, it showed lower activity on CEM cell line (IC50 10 mu mol/L) however, it was very active against Ph1-positive human leukemia BV-173 (IC50 0.91 mu mol/L) and against human myelogenous leukemia K562 (IC50 0.52 mu mol/L). Selectively labelled [3 alpha-H-2] and [3 alpha-H-3] methyl 3 beta-acetoxy-21,22-dioxolup-18-en-28-oates 24, 25 were prepared in three steps by reduction of corresponding 3-oxo derivatives and they showed moderate activity on CEM cell line (IC50 10 mu mol/L). In total, 11 labelled compounds (6-8, 11, 14, 18, 19, 21, 22, 24 and 25) have not been reported before.
    Trvalý link: http://hdl.handle.net/11104/0226393