Download coinage metal complexes containing new scorpionate

V Simposio Pharmaco-Bio-Metallics
Oral Communication
Nuovi farmaci inorganici in oncologia
COINAGE METAL COMPLEXES CONTAINING NEW SCORPIONATE
LIGANDS WITH BIOLOGICAL ACTIVITY
M. Mancini1, A. Burini2, R. Galassi2, G. Gioia Lobbia2, C. Marzano3, M. Pellei2, C. Santini2,
F. Tisato4
1. C.I.R.C.M.S.B. - Unità di Ricerca di Camerino
2. Dipartimento di Scienze Chimiche, Università di Camerino
3. Dipartimento di Scienze Farmaceutiche, Università di Padova
4. ICIS-C.N.R., Corso Stati Uniti, 4, Padova
e-mail: [email protected]
Introduction
The coordination chemistry of coinage metals with a wide variety of ligands is an important area of
chemical research because of the potential use of copper, silver and gold functionalized complexes
as therapeutic agents. Gold complexes have been used for biomedical applications in the treatment
of rheumatoid arthritis and in chemotherapy [1], and some mixed chelate copper-based drugs have
exhibited greater antineoplastic potency than cisplatin in in vitro and in vivo studies of a variety of
tumor cell lines [2].
Phosphane and phosphanoethane ligands are broadly used in the synthesis of gold, silver and copper
complexes, and they play an important role in the design and development of metal complexes for
biomedical applications and for tumoricidal properties [3].
Scorpionate ligands have been successfully used as supporting ligands for bioinorganic synthetic
studies: as an extension of the coordination chemistry of new heteroscorpionate ligands (Figure 1)
toward coinage metal acceptors, here we describe the synthesis, the spectroscopic and analytic
characterization of new scorpionate complexes containing gold(I), copper(I), silver(I) and water
soluble phosphane coligands.
H
N
N
S
C SLi
H
N
N
N
N
C
O
C OLi
H
H
C
N
N
N
N
N
N
N
O2N
Li[S2CCH(3,5-Me2Pz)2]
COONa
B
NO2
[H2B(TzNO2)2]-
Li[O2CCH(3,5-Me2Pz)2]
Figure 1. Scorpionate ligands
1
CH
N
N
N
N
N
N
Na[HC(CO2)(Tz)2]
N
V Simposio Pharmaco-Bio-Metallics
Oral Communication
Nuovi farmaci inorganici in oncologia
Results and Discussion
In order to develop specific ligand systems to produce water-soluble, kinetically inert, and in vivo
stable gold complexes, we have studied the coordination chemistry of new anionic ligands, bis(3,5dimethylpyrazol-1-yl)dithioacetate
and
bis(3,5-dimethylpyrazol-1-yl)acetate,
toward
gold(I)
complexes containing phosphane ligands such as tris(hydroxymethyl)phosphane (THP) and 1,3,5triaza-7-phosphaadamantane (TPA) [4]. Studies of biological activity are in progress in order to
obtain a structure-activity relationship for the compounds (THP)AuCl, (TPA)AuCl and
[(THP)4Au]Cl.
Moreover we have designed and synthesized the new triazole-based and water soluble bis(triazol-1yl)acetate, and the new nitro-substituted heteroscorpionate ligand, dihydridobis(3-nitro-1,2,4triazolyl)borate. New Cu(I) and Ag(I) complexes containing these scorpionates and phosphane
coligands have been synthesized and fully characterized.
The cytotoxic activity of selected hydrophilic Cu(I) complexes and the corresponding
uncoordinated ligands has also been evaluated against a panel of human tumor cell lines containing
examples of ovarian (2008), cervix (A431) and lung (A549) cancer, melanoma (A375) and
leukemia (HL60); for comparison purpose, cisplatin was tested under the same experimental
condition. All the tested Cu(I) complexes exhibited IC50 values appreciably lower than those of
cisplatin against all human tumor cell lines. Further studies are in progress to elucidate the
mechanism of action of these new class of water soluble copper complexes.
Acknowledgements
The authors are grateful to CIRCMSB for the fellowship to M. M. and to University of Camerino
for financial support (FAR).
References
[1]
[2]
[3]
[4]
C. Frank Shaw III Chem. Rev. 1999, 99, 2589-2600.
A. De Vizcaya-Ruiz, A. Rivero-Mueller, L. Ruiz-Ramırez, G.E.N. Kass, L. R. Kelland, R.M.
Orr, M. Dobrota Toxicol. In Vitro 2000, 14, 1-5.
S.J. Berners-Price, R.J. Bowen, P. Galettis, P.C. Healy, M.J. McKeage Coordin. Chem. Rev.
1999, 185-186, 823-836.
a) D. Saravana Bharathi, M.A. Sridhar, J. Shashidhara Prasad, Ashoka G. Samuelson Inorg.
Chem. Comm. 2001, 4, 490-492; b) Z. Assefa, B. G. McBurnett, R. J. Staples, J. P. Fackler Jr.
Inorg. Chem. 1995, 34, 75-83.
2