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)-triphenylphosphane-gold(i) and (4,5-dicyano-1H-imidazolate-1-yl)-triphenylphosphane-gold(i)CCDC 997733 and 997734. For crystallographic data in CIF or other electronic format see DOI: 10.1039/c4dt01542h

• Main Authors: Galassi, Rossana, Oumarou, Camille Simon, Burini, Alfredo, Dolmella, Alessandro, Micozzi, Daniela, Vincenzetti, Silvia, Pucciarelli, Stefania
• Format: Journal Article
• Language: English
• Published: 03.02.2015
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c4dt01542h

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 − , NO 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-1 H -1yl) and on the analog (triphenylphosphine)-gold( i )-(4,5-dichloroimidazolyl-1 H -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. A study on the inhibition of dihydrofolate reductase (DHFR) by gold( i ) compounds has been performed.