Dithiocarbazate complexes with the [M(PPh3)]2+ (M = Pd or Pt) moiety: synthesis, characterization and anti-Trypanosoma cruzi activity.
New neutral Pd(II) and Pt(II) complexes of the type [M(L)(PPh(3))] (M = Pd or Pt) were prepared in crystalline form in high-yield synthesis with the S-benzyldithiocarbazates and S-4-nitrobenzyldithiocarbazates derivatives from 2-hydroxyacetophenone, H(2)L(1a) and H(2)L(1b), and benzoylacetone, H(2)L(2a) and H(2)L(2b). The new complexes [Pt(L(1a))(PPh(3))] (1), [Pd(L(1a))(PPh(3))] (2), [Pt(L(1b))(PPh(3))] (3), [Pd(L(1b))(PPh(3))] (4), [Pt(L(2a))(PPh(3))] (5), [Pd(L(2a))(PPh(3))] (6), [Pt(L(2b))(PPh(3))] (7) and [Pd(L(2b))(PPh(3))] (8) were characterized on the basis of elemental analysis, conductivity measurements, UV-visible, IR, electrospray ionization mass spectrometry (ESI-MS), NMR ((1)H and (31)P) and by X-ray diffraction studies. The studies showed that differently from what was observed for the H(2)L(1a) and H(2)L(1b) ligands, H(2)L(2a) and H(2)L(2b) assume cyclic forms as 5-hydroxypyrazolinic. Upon coordination, H(2)L(2a) and H(2)L(2b) suffer ring-opening reaction, coordinating in the same manner as H(2)L(1a) and H(2)L(1b), deprotonated and in O,N,S-tridentate mode to the (MPPh(3))(2+) moiety. All complexes show a quite similar planar fourfold environment around the M(II) center. Furthermore, these complexes exhibited biological activity on extra and intracellular forms of Trypanosoma cruzi in a time- and concentration-dependent manner with IC(50) values ranging from 7.8 to 18.7 μM, while the ligand H(2)L(2a) presented a trypanocidal activity on trypomastigote form better than the standard drug benznidazole.
Maia
Pedro I da S
PI
Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil. pedovivo@iqsc.usp.br
Fernandes
André G de A
AG
Silva
Jean Jerley N
JJ
Andricopulo
Adriano D
AD
Lemos
Sebastião S
SS
Lang
Ernesto S
ES
Abram
Ulrich
U
Deflon
Victor M
VM
D000818:Animals; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D006834:Hydrazines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D056831:Coordination Complexes; D006834:Hydrazines; C010877:carbazic acid; D010984:Platinum; D010165:Palladium