Introduction

In our earlier studies, we discovered that a non-active sulphur-based ligand LH when  bound selected  metal ions, the complexes so generated  are highly active against malaria parasites¹. Although the ligand was kept constant, the biological activity varied dramatically from metal to metal. The order of the biological activity varied in the order¹ Cd>Zn>Mn>Co>Ni>standard>Fe. On the other hand, the biological activities of certain thiosemicarbazone ligand complexes of Cu(II), Ni(II) and Fe(III) were found to be less active against malaria parasites than the corresponding ligands². Also relatively recently, some diacetylferrocene-derived thiosemicarbazone ligands and their Co(II), Ni(II), Zn(II), and Cu(II) complexes³ showed good biological activity against the bacterial species E. coli, B. subtillis, S. aureus, P. aeruginosa, and S. typhi  as well as the fungal species T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glaberata. It is interesting to note that the biological activity of the ligand systems was found to be enhanced when coordinated to the metal ions³as we have found in our studies. Earlier, we discussed the paramagnetic shift influence found in the complexes Cu(LH)₂Cl₂, CuACl, and CuBCl relative to their corresponding ligands^4-5. In our continued search for biologically active compounds against malaria parasite, monoacetylferrocene-derived thiosemicarbazones ligands shown in Figures 1-3(LH, AH, and TH) and their  metal complexes[ Cu(LH)₂Cl₂, CuACl, and ZnT₂)  as well as the copper complex  (CuBCl) of the 2-acetylpyridine containing thiophenecarboxylic hydrazide moiety ligand ( see Figure 4) were synthesized and tested for the biological activity. We hereby report the findings.

Experimental

The synthesis and characterization of the ligand systems, LH, AH, BH and the complexes, Cu(LH)₂Cl₂, CuACl, and CuBCl have already been published^4-5. The synthesis and characterization of  the ligand system TH and its corresponding metal complexes will be published elsewhere.

Table 1: Biological Activity Ligand qnd Metal Complex Systems.

* SD    =  standard deviation

Figure 1 : The Structure of Ligand LH.   Click here to View figure

Figure 2 : The Structure of Ligand AH.   Click here to View figure

Figure 3 : The Structure of Ligand TH.   Click here to View figure

Figure 4 : The Structure of Ligand BH.   Click here to View figure

Results and Discussion

The results of the biological tests are shown in Table1. The biological tests against the malaria parasite were conducted in in vitro medium. Whereas the ligand systems LH, AH, and TH showed no biological activity, the corresponding metal complexes Cu(LH)₂Cl₂, CuACl and  ZnT₂ exhibited modest biological activity. This clearly indicates that in this case, the binding of the metal ions to the ligands either in their protonated or deprotonated forms enhances or activates the biological activity of the ligand. The copper(II) complex of the 2-acetylpyridine containing thiophenecarboxylic hydrazide moiety ligand, CuBCl was found to have very good biological activity against the malaria parasite. The mechanisms by which the metal ions activate the ligands  are unclear. The search for more novel complexes with sulphur-based ligands particularly the thiosemicarbazone type must be intensified.

Acknowledgement

We wish to acknowledge the University of Namibia and Petrofund Namibia for funding the work. In addition, we wish to thank the University of Cape Town for providing facilities for the spectroscopic measurements and the University of California, San Francisco, for conducting the biological tests.

References

1. M. R. Kiremire, K. Chibale, P.J. Rosenthal, L.S. Daniel, A. M. Negonga, and F. M. Munyolo, Biosciences, Biotechnology Research Asia, 4(2), 401(2007).
2. Scovill, J. P., Klayman, D. L., Lambros, C., Childs, G. E., Notsch, J. D., J. Med. Chem., 27, 87(1984).
3. H. Chohan, H. Pervez, K. M. Khan and C. T. Supuran, J. Enzyme Inhibition and Medicinal Chemistry, 20(1), 81(2005).
4. M. R. Kiremire, L. S. Daniel, H. Mu Ashekele, and H. Kambafwile, Oriental Journal of Chemistry, 23(3),785(2007).
5. M. R. Kiremire, D. S. Likius, H. Mu Ashekele, K. Chibale, and H. Kambafwile, Materials Science Research India, 4(2), 263(2007).