Synthesis and Anti-onchocercal Activity of Isonicotinoylhydrazones and their Copper(II) and Zinc(II) Complexes

Background: Onchocerciasis is one of the neglected tropical diseases with over 37 million persons affected and a risk population of over 120 million. Ivermectin, the only available drug for the treatment of onchocerciasis is microfilaricidal and there is no current drug effective against macrofilariae. The long duration of treatment of this parasite coupled with the emergence of resistance and the occurrence of severe side effects especially in cases of co-infection with Loa loa, necessitate the search for safe and more effective drug leads. Methods: Six isoniazid-derived Schiff bases were synthesized by condensation of isoniazid and various aromatic aldehydes in methanol. The complexes were synthesized in the metal to ligand molar ratio of 1:2. The ligands and the Zn(II) and Cu(II) complexes were characterized by 1H- and 13C-NMR, as well as infrared spectroscopy. Results: From the spectroscopic data, the ligands were found to coordinate to the central metal ions through the carbonyl oxygen atom as well as the azomethine nitrogen atom. The Zn(II) complexes were octahedral while the Cu(II) complexes were tetrahedral. The ligands and their Zn(II) complexes were inactive against microfilaria while the Cu(II) complexes showed significant activity against both micro- and macrofilaria with IC50 values of 5 μg/mL and 10 μg/mL respectively. Conclusion: The Cu(II) complexes are potential targets for the development of more effective anti-onchocercal agents. This is the first report of the anti-onchocercal activity of these isoniazid-derived Schiff bases and their complexes.