Synthesis and characterization of copper(II) complexes of pyridine-2-carboxamidrazones as potent antimalarial agents

• Published in: Inorganica Chimica Acta 2003-06, Vol.349, p.23-29
• Main Authors: Gokhale, Nikhil H., Padhye, Subhash B., Billington, David C., Rathbone, Daniel L., Croft, Simon L., Kendrick, Howard D., Anson, Christopher E., Powell, Annie K.
• Format: Article
• Language: English
• Subjects: Antimalarial; Carboxamidrazones; Copper; Plasmodium falciparum
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/S0020-1693(03)00047-1

Copper(II) complexes of some pyridine-2-carboxamidrazones have been prepared and characterized. The crystal structures of the copper complex cis-[dichloro(N 1-2-acetylthiophene-pyridine-2-carboxamidrazone)copper(II)] 8a and one of the free ligands, viz. {( p-chloro-2-thioloxy-benzylidine-pyridine-2-carboxamidrazone)} 6, have been determined. The former shows a highly distorted square planar geometry around copper, with weak intermolecular coordination from the thiophenyl sulfur resulting in a stacking arrangement in the crystal lattice. The in vitro activities of the synthesized compounds against the malarial parasite Plasmodium falciparum are reported for the first time, which clearly shows the advantage of copper complexation and the requirement of four coordinate geometry around copper as some of the key structural features for designing such metal-based antimalarials. New copper(II) complexes of pyridine-2-carboxamidrazone ligands have been synthesized and characterized. The evaluation of in vitro antimalarial activity of the ligands and their copper complexes clearly shows the advantage of metal conjugation in the design of an antimalarial agent.