Solvent and Copper Ion-Induced Synthesis of Pyridyl-Pyrazole-3-One Derivatives: Crystal Structure, Cytotoxicity

Five novel compounds, methyl 5-(acetyloxy)-1-(6-bromo-2-pyridinyl)-1H-pyrazole-3-carboxylate (1), methyl 1-(6-bromo-2-pyridinyl)-5-hydroxy-1H-pyrazole-3-carboxylate (2), Trimethyl 1,1',1''-tris(6-bromo-2-pyridinyl)-5,5''-dihydroxy-5'-oxo-1',5'-dihydro-1H,1''H-4,4': 4',4''-terpyrazole-3,3',3''-tricarboxylate (H₂L¹, 3), [Cu₂(L²)₂]·CH₃OH (4), H₂L^2A·CH₃CN (5) were synthesized. Compounds 1-5 characterized by elemental analysis, IR, and X-ray single-crystal diffraction. And 1-3 were also characterized by ¹H NMR, ¹³C NMR and ESI-MS. The H₂L¹, H₂L² were formed by in-situ reaction. H₂L² and H₂L^2A are mesomer compounds which have two chiral carbons. The antitumor activity of compounds 1-5 against BEL-7404, HepG2, NCI-H460, T-24, A549 tumor cell lines were screened by methylthiazolyl tetrozolium (MTT) assay. The compounds 1, 2 showed weakly growth inhibition on the HepG2 cell lines. The HepG2 and A549 cell lines showed higher sensitivity to compound 4, while the IC₅₀ values are 10.66, 28.09 μM, respectively. It is worth noting that compounds 1-5 did not show cytotoxicity to human normal liver cell line HL-7702, suggesting its cytotoxic selectivity on these tumor cell lines.