Book of Abstracts - Ruhr-Universität Bochum

P-04
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Organometallic Palladium(II) Complexes Containing Tridentate [C,N,S]
Thiosemicarbazone Ligands: Synthesis, Structure and Antimalarial activity
Prinessa Chellan, a Kelly Chibale, a,b and Gregory S. Smith *a
a University of Cape Town, Faculty of Science, Department of Chemistry, Private Bag, Rondebosch
7701, South Africa, b Institute of Infectious Disease and Molecular Medicine, University of Cape
Town, Rondebosch 7701, South Africa. E-mail: prinessa.chellan@uct.ac.za
Thiosemicarbazones (TSCs) are Schiff base type compounds that are noted for their pharmacological
properties, particularly as antiparisital, 1 antibacterial 2 and antitumoral agents. 3 The antiplasmodial
activity of thiosemicarbazones against Plasmodium falciparum strains has been reported. 4 However,
reports on the use of thiosemicarbazone metal complexes as antimalarial agents are sparse.
In this presentation, we report the synthesis, characterisation and antimalarial study of mono-, di- and
tetrameric cyclopalladated [C,N,S] Pd(II) complexes prepared from two thiosemicarbazone ligands,
3,4-dichloroacetophenone thiosemicarbazone (1, Scheme 1) and 3,4-dichloropropiophenone
thiosemicarbazone (2), which have previously been screened for biological activity. 5 Attendant
questions to be addressed in this presentation are, whether coordination of these compounds to
palladium enhances their inhibitory effects and if the number of thiosemicarbazone Pd(II) complex
moieties per molecule would increase antiplasmodial activity.
References
Cl
Cl
4
3
Scheme 1
5
2
1
R
Cl
Cl
N
Pd
Cl
Cl
PPh 3
4
3
PPh 3 / Acetone
5: R = CH 3
6: R = CH 2CH 3
N NH 2
S
5
2
R
R
N
H
N NH 2
6
N
N NH2 3: R = CH3 4: R = CH2CH3 1
Pd S
Cl
R
5
62
S
K 2[PdCl 4] / EtOH-H 2O
4
6
3
N
R.T.
Cl
N
1
2
4
P P / Acetone
Pd
S
NH 2
P
1: R = CH 3
2: R = CH 2CH 3
P
H 2N
S
P P = bis(diphenylphoshino)ferrocene (7 and 8);
trans-bis(diphenylphosphino)ethylene (9 and 10);
bis(diphenylphosphino)benzene (11 and 12)
Pd
N
Cl
N
7, 9, 11: R = CH 3
8, 10, 12: R = CH 2CH 3
1. K. J. Duffy, A. N. Shaw, E. Delorme, S. B. Dillon, C. Erickson-Miller, L. Giampa, Y. Huang, R. M. Keenan,
P. Lamb, N. Liu, S. G. Miller, A. T. Price, J. Rosen, H. Smith, K. J. Wiggall, L. Zhang and J. I. Luengo, J.
Med. Chem. 2002, 45, 3573-3578.
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Chem. 2002, 45, 2695-2707.
3. D. Kovala-Demertzi, M.A. Demertzis, E. Filou, A.A Pantazaki, P.N. Yadav, J.R. Miller, Y. Zheng and D.A.
Kyriakidis, Biometals 2003, 16, 411-418.
4. For example, A. Walcourt, M. Loyevsky, D. B. Lovejoy, V. R. Gordeuk and D. R. Richardson, Int. J.
Biochem. Cell Biol. 2004, 36, 401-407.
5. For example, N. Fujii, J. P. Mallari, E. J. Hansell, Z. Mackey, P. Doyle, Y. M. Zhou, J. Gut, P. J. Rosenthal,
J. H. McKerrow and R. K. Guy, Bioorg. Med. Chem. Lett. 2005, 15, 121-123.
R
Cl