Synthesis, spectroscopy (IR, multinuclear NMR, ESI-MS), diffraction, density functional study and in vitro antiproliferative activity of pyrazole-beta-diketone dihalotin(IV) compounds on 5 melanoma cell lines

Novel 4-acylpyrazolon-5-ato-dihalotin(IV) complexes, [Q₂SnX ₂], (X = F, Cl, Br or I); HQ = HQ^CHPh2 (1,2-dihydro-3-methyl-1-phenyl-4-(2,2-diphenylacetyl)pyrazol-5-one), HQ ^Bn (1,2-dihydro-3-methyl-1-phenyl-4-(2-phenylacetyl)pyrazol-5-one) or HQ^CF3,py (4-(2,2,2-trifluoroacetyl)-1,2-dihydro-3-methyl-1-(pyridin- 2-yl)pyrazol-5-one) have been synthesized and characterized by spectroscopic (IR, ¹H, ¹³C, ¹⁹F and ¹¹⁹Sn NMR, electrospray ionisation mass spectrometry (ESI-MS)), analytical and structural methods (X-ray and density functional theory). ¹¹⁹Sn chemical shifts depend on the nature of the halides bonded to tin. Isomer conversion, detected in solution by NMR spectroscopy, is related to the acyl moiety bulkiness while the cis(Cl)-cis(acyl)-trans(pyrazolonato) scheme is found in the solid state. The in vitro antiproliferative tests of three derivatives on three human melanoma cell lines (JR8, SK-MEL-5, MEL501) and two melanoma cell clones (2/21 and 2/60) show dose-dependent decrease of cell proliferation in all cell lines. The activity correlates with the nature of the substituent on position 1 of pyrazole, decreasing in the order pyridyl > Ph ≫ methyl. The activity for (Q^CF3,py)₂SnCl₂ on the SK-MEL-5 cell line is IC₅₀ = 50 μM.