Pyrazole-based lamellarin O analogues: synthesis, biological evaluation and structure–activity relationships

Karolina Dzedulionytė, Nina Fuxreiter, Ekaterina Schreiber-Brynzak, Asta Žukauskaitė, Algirdas Šačkus, Verena Pichler, Eglė Arbačiauskienė

Publications: Contribution to journalArticlePeer Reviewed

Abstract

A library of pyrazole-based lamellarin O analogues was synthesized from easily accessible 3(5)-aryl-1H-pyrazole-5(3)-carboxylates which were subsequently modified by bromination, N-alkylation and Pd-catalysed Suzuki cross-coupling reactions. Synthesized ethyl and methyl 3,4-diaryl-1-(2-aryl-2-oxoethyl)-1H-pyrazole-5-carboxylates were evaluated for their physicochemical property profiles and in vitro cytotoxicity against three human colorectal cancer cell lines HCT116, HT29, and SW480. The most active compounds inhibited cell proliferation in a low micromolar range. Selected ethyl 3,4-diaryl-1-(2-aryl-2-oxoethyl)-1H-pyrazole-5-carboxylates were further investigated for their mode of action. Results of combined viability staining via Calcein AM/Hoechst/PI and fluorescence-activated cell sorting data indicated that cell death was triggered in a non-necrotic manner mediated by mainly G2/M-phase arrest.

Original languageEnglish
Pages (from-to)7897-7912
Number of pages16
JournalRsc advances
Volume13
Issue number12
DOIs
Publication statusPublished - 2023

Austrian Fields of Science 2012

  • 104015 Organic chemistry

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