An unprecedented study on the inhibitory activities of a class of phosphane gold(I) complexes on E. coli dihydrofolate reductase (DHFR) is reported. The gold(I) complexes considered in this work consist of azolate or chloride ligands and phosphane as co-ligands. The ligands have been functionalized with polar groups (–COOH, –COO−, NO2, Cl, CN) to obtain better solubility in polar media. Neutral, anionic and cationic gold(I) complexes have been tested as DHFR inhibitors by means of a continuous direct spectrophotometric method. X-ray structural characterizations were performed on ((triphenylphosphine)-gold(I)-(4,5-dicyanoimidazolyl-1H-1yl) and on the analog (triphenylphosphine)-gold(I)-(4,5-dichloroimidazolyl-1H-1yl). The inhibition constants obtained from the enzyme tests range from 20 μM to 63 nM (auranofin) and are conducive to promoting these compounds as potential DHFR inhibitors.
