Copper complexes of nicotinic-aromatic carboxylic acids as superoxide dismutase mimetics.
Nicotinic acid (also known as vitamin B3) is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids). The tested copper complexes exhibited superoxide dismutase (SOD) mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 microg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph) was the most potent with a SOD mimetic activity of IC(50) 34.42 microM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT) at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA) value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics.
Suksrichavalit
Thummaruk
T
Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand. rukmu47@gmail.com
Prachayasittikul
Supaluk
S
Piacham
Theeraphon
T
Isarankura-Na-Ayudhya
Chartchalerm
C
Nantasenamat
Chanin
C
Prachayasittikul
Virapong
V
D000890:Anti-Infective Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D006841:Hydrocarbons, Aromatic / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009525:Niacin / Q000737:chemistry* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D000890:Anti-Infective Agents; D002264:Carboxylic Acids; D016166:Free Radical Scavengers; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D013481:Superoxides; D009525:Niacin; D003300:Copper; D013482:Superoxide Dismutase