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, [Q2SnX2], (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 microM.
Pettinari
Claudio
C
Università di Camerino, Dipartimento Scienze Chimiche, Via S Agostino 1, 62032, Camerino (MC), Italy. claudio.pettinari@unicam.it
Caruso
Francesco
F
Zaffaroni
Nadia
N
Villa
Raffaella
R
Marchetti
Fabio
F
Pettinari
Riccardo
R
Phillips
Christine
C
Tanski
Joseph
J
Rossi
Miriam
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013055:Spectrophotometry, Infrared / Q000379:methods*; D017971:Tin Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011720:Pyrazoles; D017971:Tin Compounds