Počet záznamů: 1
Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines
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SYSNO ASEP 0489492 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines Tvůrce(i) Milišiunaitė, V. (LT)
Arbačiauskienė, E. (LT)
Řezníčková, Eva (UEB-Q) RID, ORCID
Jorda, Radek (UEB-Q) ORCID, RID
Malínková, V. (CZ)
Žukauskaitė, Asta (UEB-Q) ORCID
Holzer, W. (AT)
Šačkus, A. (LT)
Kryštof, Vladimír (UEB-Q) RID, ORCIDCelkový počet autorů 9 Zdroj.dok. European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234
Roč. 150, APR 25 (2018), s. 908-919Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. FR - Francie Klíč. slova Apoptosis ; G2/M cell cycle arrest ; Pyrazole ; Structure-activity relationships Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology CEP LO1204 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UEB-Q - RVO:61389030 UT WOS 000430891400066 EID SCOPUS 85044457789 DOI 10.1016/j.ejmech.2018.03.037 Anotace An efficient synthetic route for the synthesis of 2H-pyrazolo[4,3-c]pyridines, primarily varying by the substituents at the 2-, 4- and 6-positions, is described here. A Sonogashira-type cross-coupling reaction was employed to yield 3-alkynyl-1H-pyrazole-4-carbaldehydes, ethanones and propanones from the corresponding 1H-pyrazol-3-yl trifluoromethanesulfonates. Subsequent treatment of the coupling products with dry ammonia afforded a versatile library of 2H-pyrazolo[4,3-c] pyridines, which were then evaluated for their cytotoxicity against K562 and MCF-7 cancer cell lines. The most potent of these compounds displayed low micromolar GI 50 values in both cell lines. Active compounds induced dose-dependent cell-cycle arrest in mitosis, as shown by flow cytometric analysis of DNA content and phosphorylation of histone H3 at serine-10. Moreover, biochemical assays revealed increased activities of caspases-3/7 in treated cells, specific fragmentation of PARP-1, and phosphorylation of Bcl-2, collectively confirming apoptosis as the mechanism of cell death. Pracoviště Ústav experimentální botaniky Kontakt David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Rok sběru 2019
Počet záznamů: 1