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Published on: June 23, 2019
Pyrazole-based lamellarin O analogues: synthesis, biological evaluation and structure-activity relationships
Karolina Dzedulionytė1, Nina Fuxreiter2, Ekaterina Schreiber-Brynzak2
1Department of Organic Chemistry, Faculty of Chemical Technology, Kaunas University of Technology Radvilėnų pl. 19 LT-50254 Kaunas Lithuania egle.arbaciauskiene@ktu.lt.
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.
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