Book of Abstracts - Ruhr-Universität Bochum

P-68
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Study of Interaction of Gold Drugs with Thiols
Using Various Analytical Techniques
Gohar T. Kazimi a* and Mohammad S Iqbal b
a Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan. E-mail:
gohartaqi@hotmail.com
b Department of Chemistry, GC University, Lahore 54000, Pakistan. E-mail: saeediq50@hotmail.com
Since ancient times, gold has occupied a special place in medicine to cure diseases. Now a days gold
based drugs are being used in the treatment of an autoimmune inflammatory disease known as
rheumatoid arthritis (RA). 1 Solganal TM (gold thioglucose), Myochrisine TM (gold sodium thiomalate)
and Ridaura TM (auranofin, 2,3,4,6-tetraacetyl-β-1-D-thiogluco-pyranosato-S-(triethyl phosphine)gold(I),
Et3PAuStagl) are used for the treatment of this disease but their mode of action is still
uncertain. Furthermore, several studies have demonstrated that several gold (I) and gold (III) salts also
exhibit anti-tumour activities. 2-4 The pharmacokinetic and pharmacological properties of these drugs
mainly depend upon ligands present on them and various studies have shown that these ligands are
replaced in the body by some endogenous molecules. 1
In this work some of the ligand exchange reactions of gold drugs with various thiols including
cysteine, glutathione, N-acetylcysteine and O-methylcysteine were studied in both solution and in
solid state. Various analytical techniques like ESI-MS, DESI-MS, pXRD and FT-IR used in this study
confirmed the ligand exchange mechanism. ESI-MS was successfully employed for characterization of
the ligand-exchange products. When cysteine reacts with auranofin in solution, the formation of
[Et3PAuSCy] – (m/z = 434), [taglSAuCyS] – (m/z = 680) and [Au(Stagl)2] – (m/z = 923) were observed
along with [Au(PEt3)2] + (m/z =433) in the positive-ion spectrum. Similarly with O-methylcysteine the
formation of [TaglSSOMeCy] – (m/z = 497), [taglSAuSOMeCyS] – (m/z = 694), [Au(Stagl)2] – (m/z =
923) and [Et3PAuSOMeCy] + (m/z =450) indicated the ligand exchange during reaction. DESI-MS,
pXRD and FT-IR were found to be helpful in characterization the products of the reactions performed
in the solid state.
This study provides very useful information in understanding the in vivo biochemistry of the gold
drugs used for rheumatoid arthritis.
References
1. C.F. Shaw, III, Chem. Rev. 1999, 99, 2589-2600.
2. E.R.T. Tiekink, P.D. Cookson, B.M. Linahan, L.K. Webster, Metal-Based Drugs 1994, 1,299.
3. L.K.Webster, S. Rainone, E. Horn, E.R.T. Tiekink, Metal-Based Drugs 1996, 3, 63.
4. D. Crump, G. Siasios, E.R.T. Tiekink, Metal-Based Drugs 1999, 6, 361.
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