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.

Department of Chemical Biology Faculty of Science Palacký University Šlechtitelů 27 CZ 78371 Olomouc Czech Republic

Department of Organic Chemistry Faculty of Chemical Technology Kaunas University of Technology Radvilėnų pl 19 LT 50254 Kaunas Lithuania

Department of Pharmaceutical Sciences Division of Pharmaceutical Chemistry Faculty of Life Sciences University of Vienna Althanstraße 14 1090 Vienna Austria

Institute of Synthetic Chemistry Faculty of Chemical Technology Kaunas University of Technology K Baršausko g 59 LT 51423 Kaunas Lithuania

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