TY - JOUR
T1 - Pyrazole-based lamellarin O analogues: synthesis, biological evaluation and structure–activity relationships
AU - Dzedulionytė, Karolina
AU - Fuxreiter, Nina
AU - Schreiber-Brynzak, Ekaterina
AU - Žukauskaitė, Asta
AU - Šačkus, Algirdas
AU - Pichler, Verena
AU - Arbačiauskienė, Eglė
N1 - Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85150598128&partnerID=8YFLogxK
U2 - 10.1039/D3RA00972F
DO - 10.1039/D3RA00972F
M3 - Article
SN - 2046-2069
VL - 13
SP - 7897
EP - 7912
JO - Rsc advances
JF - Rsc advances
IS - 12
ER -