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Anticancer 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5<i>H</i>)‐ones as tubulin inhibitors

Jiřı́ Řehulka, Ivanna Subtel’na, Anna Kryshchyshyn‐Dylevych, Alina Cherniienko, Aleksandra Ivanová, Mariia Matveieva, Pavel Polishchuk, Soňa Gurská, Marián Hajdúch, Oleh Zagrijtschuk, Petr Džubák, Roman Lesyk

2022Archiv der Pharmazie13 citationsDOI

Abstract

Abstract Studying the anticancer activity of 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5 H )‐ones towards cell lines of different cancer types allowed the identification of hit‐compounds inhibiting the growth of daunorubicin‐ (CEM‐DNR, IC 50 = 0.32–1.28 µM) and paclitaxel‐resistant (K562‐TAX, IC 50 = 0.21–1.23 µM) cell lines, with favorable therapeutic indexes. The studied compounds induced apoptosis and cellular proliferation in treated CCRF‐CEM cells. The hit compounds were shown to induce mitotic arrest by interacting with tubulin, inhibiting its polymerization by binding to the colchicine binding site.

Topics & Concepts

TubulinDaunorubicinChemistryColchicinePaclitaxelMicrotubuleCell growthCell cultureIC50K562 cellsStereochemistryApoptosisAntimitotic AgentPharmacologyBiochemistryIn vitroCancerBiologyChemotherapyCell biologyGeneticsSynthesis and biological activityQuinazolinone synthesis and applicationsSynthesis and Characterization of Heterocyclic Compounds