Gold(I) Based Drugs are a bet for researchers who are involved in the field of bioinorganic chemistry of late transition metals. Although their therapeutic effect is well known and their efficacy against complex diseases such as rheumatoid arthritis or cancer is well established, the serious side effects observed as well as the lack of understanding of the mechanisms of action, causes these promising compounds have not yet found their place in the panorama of metal-based drugs. Recently, we have reported some studies about a good cytotoxic activity of some pyrazolate gold(I) phosphane complexes and the possible involvement of the inhibition of thioredoxine reductase in their mechanism of action. They show interesting anticancer properties against several panel of cancer cells. Moreover, a parallel study on the inhibition of the enzyme dihydrofolate reductase (DHFR) was performed, showing that these compounds inhibit DHFR with binding constant in the range of micromolar order of magnitude. By this study a possible role of this enzyme as putative target in the mechanism of action of gold(I) based drugs has been evidenced.
Imidazolate Gold(I) Phosphane complexes as potential anticancer drugs acting as inhibitors of DHFR
GALASSI, Rossana;BURINI, Alfredo;SANTINI, Carlo;PELLEI, Maura;RICCI, SIMONE;PUCCIARELLI, Stefania
2011-01-01
Abstract
Gold(I) Based Drugs are a bet for researchers who are involved in the field of bioinorganic chemistry of late transition metals. Although their therapeutic effect is well known and their efficacy against complex diseases such as rheumatoid arthritis or cancer is well established, the serious side effects observed as well as the lack of understanding of the mechanisms of action, causes these promising compounds have not yet found their place in the panorama of metal-based drugs. Recently, we have reported some studies about a good cytotoxic activity of some pyrazolate gold(I) phosphane complexes and the possible involvement of the inhibition of thioredoxine reductase in their mechanism of action. They show interesting anticancer properties against several panel of cancer cells. Moreover, a parallel study on the inhibition of the enzyme dihydrofolate reductase (DHFR) was performed, showing that these compounds inhibit DHFR with binding constant in the range of micromolar order of magnitude. By this study a possible role of this enzyme as putative target in the mechanism of action of gold(I) based drugs has been evidenced.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
