Počet záznamů: 1
Synthesis of selectively deuterated and tritiated lupane derivatives with cytotoxic activity
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SYSNO ASEP 0398914 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Synthesis of selectively deuterated and tritiated lupane derivatives with cytotoxic activity Tvůrce(i) Vlk, M. (CZ)
Urban, M. (CZ)
Elbert, Tomáš (UOCHB-X) RID, ORCID
Šarek, J. (CZ)Celkový počet autorů 4 Zdroj.dok. Journal of Radioanalytical and Nuclear Chemistry. - : Springer - ISSN 0236-5731
Roč. 298, č. 2 (2013), s. 1149-1157Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. HU - Maďarsko Klíč. slova isotopic labelling ; tritium ; deuterium ; betulin ; betulinic acid ; cytotoxicity Vědní obor RIV CB - Analytická chemie, separace Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000325624300049 EID SCOPUS 84885953073 DOI 10.1007/s10967-013-2533-8 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Rok sběru 2014
Počet záznamů: 1