title: 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).
abstract: 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.
authors.affiliation: School of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino, 1, 62032 Camerino, Italy. rossana.galassi@unicam.it.
authors.forename: Rossana
authors.initials: R
authors.lastname: Galassi
authors.forename: Camille Simon
authors.initials: CS
authors.lastname: Oumarou
authors.forename: Alfredo
authors.initials: A
authors.lastname: Burini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dolmella
authors.forename: Daniela
authors.initials: D
authors.lastname: Micozzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Vincenzetti
authors.forename: Stefania
authors.initials: S
authors.lastname: Pucciarelli
mesh_terms: D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D005493:Folic Acid Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006046:Gold / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010720:Phosphines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D005493:Folic Acid Antagonists; D010720:Phosphines; D006046:Gold; D013762:Tetrahydrofolate Dehydrogenase; C044646:phosphine