Multi-Targeted Anticancer Activity of Imidazolate Phosphane Gold(I) Compounds by Inhibition of DHFR and TrxR in Breast Cancer Cells

A class of phosphane gold(I) compounds, made azoles and ligands, was evaluated for a screening on the regards Breast Cancer cell panels (BC). The compounds possess N-Au-P or Cl-Au-P bonds around central metal, they differ presence aprotic protic polar groups in and/or moieties to tune their hydrophilicity. Among six candidates, only having P-Au-N environment not displaying neither hydroxyl nor carboxyl ligands were found active. screened by MTT tests SKBR3, A17, MDA-MB231 cancer cells, two (namely 4,5-dicyano-imidazolate-1yl-gold(I)-(triphenylphosphane, 5, 4,5-dichloro-imidazolate-1yl-gold(I)-triphenylphosphane, 6) very cytotoxic, with most active an IC 50 value 3.46 μM cells. By performing enzymatic assays treated cells lysates, residual activity dihydrofolate reductase (DHFR) has been measured after treatment 4 12 h comparison control Upon treatment, DHFR significantly reduced both SKBR3 A17 5 6, but human cells; interestingly, it remarkably high revealing time dependence assays. inhibition data have compared those thioredoxin (TrxR), recognized molecular target gold compounds. For this latter, similar activities (i.e., 37 49% match compound respectively) found. Binding studies ct-DNA (calf-thymus-DNA) plasma transporters proteins, such as BSA (bovine serum albumin) ATF (apo transferrin), performed. As expected support strong binding proteins (K sv values range: 1.51 ÷ 2.46 × 10 M −1 ) weaker interaction ct-DNA's minor groove 1.55 6.12 3 ).