Pd(II) and Pt(II) complexes of trimethoprim and pyrimethamine were synthesized and characterized by elemental analysis, UV-Vis, FTIR, and NMR spectroscopy. The complexes are formulated as four coordinate square planar species containing two molecules of the drugs and two chloride or thiocyanate ions. The coordination of the metal ions to the pyrimidine nitrogen atom of the drugs was confirmed by spectroscopic analyses. The complexes were screened for their antibacterial activities against eight bacterial isolates. They showed varied activities with the active metal complexes showing more enhanced inhibition than either trimethoprim or pyrimethamine. The Pd(II) complexes of pyrimethamine showed unique inhibitory activities against P. aeruginosa and B. pumilus, and none of the other complexes or the drugs showed any activity against these bacteria isolates. The MIC and MBC determinations revealed that these Pd(II) complexes are the most active. Structure activity relationship showed that Pt(II) complexes containing chloride ions are more active, while for Pd(II) complexes containing thiocyanate ions showed more enhanced activity than those containing chloride ions. 1. Introduction The discovery of potent group of pyrimidines with pronounced antagonistic effect on folic acid in cultures of Lactobacilli [1] led to the development of pyrimethamine and trimethoprim. Pyrimethamine was developed through brilliant feet of organic synthesis guided by biochemical considerations [2]. Additional modifications led to the synthesis of trimethoprim that inhibits bacterial dihydrofolate reductase like other diaminopyrimidines and its consequence selection as antibacterial agent [3–5]. Trimethoprim is a broad-spectrum antimicrobial and also exhibits antiparasitic activities [6]. Due to intensive use and misuse, resistance has emerged against trimethoprim [7]. Development of antimicrobial drugs was hailed as one of the great medical success story of the twentieth century [8]. At present, resistance against antimicrobial agents have become public health problem worldwide [9–15]. In the search for novel drugs against drug resistant diseases, the use of metal complexes has received tremendous attention [16–24] and resulted in a variety of exciting and invaluable drugs such as cis-platin [24]. Research are being undertaken in fields such as cancer [25–27], diabetes [28–32], arthritis [33], magnetic resonance imaging [34], metal-mediated antibiotics, antibacterial, antiviral, antiparasitic and radiosensitizers [35–38]. In continuation of our efforts [39–44] to develop
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