A study on the inhibition of dihydrofolate reductase (DHFR) from Escherichia coli by gold(i) phosphane compounds. X-ray crystal structures of (4,5-dichloro-1H-imidazolate-1-yl)-triphenylphosph ane-gold(i) and (4,5-dicyano-1H-imidazolate-1-yl)-triphenylphospha ne-gold(i)

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 super(-), NO sub(2), 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 mu M to 63 nM (auranofin) and are conducive to promoting these compounds as potential DHFR inhibitors.