Coordination to copper(II) strongly enhances the in vitro antimicrobial activity of pyridine-derived N(4)-tolyl thiosemicarbazones

Five copper(II) complexes with N(4)-ortho, N(4)-meta and N(4)-para-tolyl thiosemicarbazones derived from 2-formyl and 2-acetylpyridine were obtained and thoroughly characterized. The crystal structure of N(4)-meta-tolyl-2-acetylpyridine thiosemicarbazone (H2Ac4mT) was determined, as well as that of its copper(II) complex [Cu(2Ac4mT)Cl], which contains an anionic ligand and a chloride in the coordination sphere of the metal. The in vitro antimicrobial activities of all thiosemicarbazones and their copper(II) complexes were tested against Salmonella typhimurium and Candida albicans. Upon coordination a substantial decrease in the minimum inhibitory concentration, from 225 to 1478 μmol L−1 for the thiosemicarbazones to 5–30 μmol L−1 for the complexes was observe against the growth of Salmonella typhimurium and from 0.7–26 to 0.3–7 μmol L−1 against the growth of C. albicans, suggesting that complexation to copper(II) could be an interesting strategy of dose reduction.

Graphical abstractCopper(II) complexes with N(4)-ortho, N(4)-meta and N(4)-para-tolyl thiosemicarbazones derived from 2-formyl and 2-acetylpyridine were obtained. The crystal structures of N(4)-meta-tolyl-2-acetylpyridine thiosemicarbazone (H2Ac4mT) and its complex [Cu(2Ac4mT)Cl] were determined. Upon coordination a substantial decrease in the minimum inhibitory concentration was observed against the growth of Salmonella typhimurium, from 225 to 1478 μmol L−1 for the thiosemicarbazones to 5–30 μmol L−1 for the complexes, and against the growth of Candida albicans, from 0.7–26 to 0.3–7 μmol L−1, suggesting that complexation to copper(II) could be an interesting strategy of dose reduction.Figure optionsDownload full-size imageDownload as PowerPoint slide