Simple 2(5H)-furanone derivatives with selective cytotoxicity towards non-small cell lung cancer cell line A549 – Synthesis, structure-activity relationship and biological evaluation
2018; Elsevier BV; Volume: 150; Linguagem: Inglês
10.1016/j.ejmech.2018.03.021
ISSN1768-3254
AutoresAnna Byczek-Wyrostek, Radosław Kitel, Klaudia Rumak, Magdalena Skonieczna, Anna Kasprzycka, Krzysztof Walczak,
Tópico(s)Carbohydrate Chemistry and Synthesis
ResumoA series of 5-alkoxy derivatives of 3,4-dichloro-5-hydroxyfuran-2-(5H)-one (mucochloric acid, MCA) were obtained and subsequently subjected to modification in the C-4 position of 2(5H)-furanone ring. The cytotoxicity of newly synthesized compounds was evaluated in MTT assay against non-small cell lung cancer (A549) and healthy lung epithelial cell line (BEAS-2B). The derivatives containing a branched alkoxy substituent in the C-5 position demonstrated the highest anticancer properties, whereas modification of compounds in the C-4 position of 2(5H)-furanone ring only slightly improve their antiproliferative properties. Compounds 12 and 15 exhibited the best selectivity towards A549 cells and were also evaluated in a panel of cancer cell lines of different origin. Further investigation revealed that treatment of A549 cell line with compounds 12 and 15 led to G2 phase cell cycle arrest and induction of caspase-independent cell death. Moreover, compound 12 was found to act synergistically with erlotinib.
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