Copper complexes of pyridine derivatives with superoxide scavenging and antimicrobial activities

Superoxide anions are reactive oxygen species that can attack biomolecules such as DNA, lipids and proteins to cause many serious diseases. This study reports the synthesis of copper complexes of nicotinic acid with related pyridine derivatives. The copper complexes were shown to possess superoxide dismutase (SOD) and antimicrobial activities. The copper complexes exerted SOD activity in range of 49.07–130.23 μM. Particularly, copper complex of nicotinic acid with 2-hydroxypyridine was the most potent SOD mimic with an IC50 of 49.07 μM. In addition, the complexes exhibited antimicrobial activity against Bacillus subtilis ATCC 6633 and Candida albicans ATCC 90028 with MIC range of 128–256 μg/mL. The SOD activities were well correlated with the theoretical parameters as calculated by density functional theory at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complexes was demonstrated to be inversely correlated with the electron affinity, but was well correlated with both HOMO and LUMO energies. The vitamin–metal complexes described in this report are great examples of the value-added benefits of vitamins for medicinal applications.

Copper coordination complexes of nicotinic acid (also known as vitamin B3) and related pyridine derivatives (e.g. 2-hydroxypyridine, 2-aminopyridine and picolinic acid) were prepared and evaluated for superoxide dismutase and antimicrobial activities. Theoretical parameters derived from low energy conformers calculated at B3LYP/LANL2DZ level were demonstrated to be inversely correlated with the electron affinity, but were well correlated with both HOMO and LUMO energies (r = 0.97 and 0.99). Such compounds demonstrate good prospects for novel therapeutic applications as superoxide radical scavengers and antimicrobials.Figure optionsDownload as PowerPoint slide