Galassi Rossana, Oumarou Camille Simon, Burini Alfredo, Dolmella Alessandro, Micozzi Daniela, Vincenzetti Silvia, Pucciarelli Stefania
School of Science and Technology, Chemistry Division, University of Camerino, Via S. Agostino, 1, 62032 Camerino, Italy.
Dalton Trans. 2015 Feb 21;44(7):3043-56. 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(-), 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.
报道了一项关于一类膦金（I）配合物对大肠杆菌二氢叶酸还原酶（DHFR）抑制活性的前所未有的研究。本研究中考虑的金（I）配合物由唑酸盐或氯配体以及膦作为共配体组成。这些配体已用极性基团（-COOH、-COO（-）、NO2、Cl、CN）进行功能化，以在极性介质中获得更好的溶解性。通过连续直接分光光度法对中性、阴离子和阳离子金（I）配合物作为DHFR抑制剂进行了测试。对（（三苯基膦）-金（I）-（4,5-二氰基咪唑基-1H-1基）和类似物（三苯基膦）-金（I）-（4,5-二氯咪唑基-1H-1基）进行了X射线结构表征。酶测试获得的抑制常数范围为20μM至63 nM（金诺芬），有利于将这些化合物推广为潜在的DHFR抑制剂。
