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 (H(2)L(1), 3), [Cu(2)(L(2))(2)]·CH(3)OH (4), H(2)L(2A)·CH(3)CN (5) were synthesized. Compounds 1–5 characterized by elemental analysis, IR, and X-ray single-crystal diffraction. And 1–3 were also characterized by (1)H NMR, (13)C NMR and ESI-MS. The H(2)L(1), H(2)L(2) were formed by in-situ reaction. H(2)L(2) and H(2)L(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 IC(50) 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.