Selective Anticancer and Antimicrobial Metallodrugs Based on Gold(III) Dithiocarbamate Complexes

Abstract

New dithiocarbamate cycloaurated complexes have been synthesized and their physicochemical and in vitro antitumor properties have been evaluated. All the performed studies highlighted good transport through the blood and biodistribution, according to the balance between the properties of hydrophilicity/lipophilicity and the binding of moderate strength to the BSA protein. Furthermore, none of the complexes exhibited reduction or decomposition reactions, presenting excellent physiological stability. The in vitro cytotoxic effect was evaluated on human colon cancer cell line Caco-2/TC7, and the complexes showed great antiproliferative activity and excellent selectivity, as much less effect was detected on normal Caco-2/TC7 cells. Most of the complexes exhibit antiproliferative activity that was better than or similar to auranofin, and at least nine times better than that of cisplatin. Its action mechanism is still under discussion since no evidence of cell cycle arrest was found, but an antioxidant role was shown for some of the selective complexes. All complexes were also tested as antimicrobial drugs, exhibiting good activity towards S. aureus and E. coli. bacteria and C. albicans and C. neoformans fungi.

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…The cytotoxicity of the human colon cancer cell line Caco-2/TC7 was evaluated in vitro , and complex 335 showed the best antiproliferative activity and excellent selectivity, with IC 50 values of 1.85 ± 0.36 μM for Caco-2/TC7 cells and 12.95 ± 0.11 μM for normal cells. 241 Khodjoyan et al synthesized and characterized several cationic gold( iii ) complexes with the general formula [(C^C)Au(N^N)]. The results showed that complex 336 (IC 50 = 0.12 ± 0.03 μM for A2780, 0.15 ± 0.01 μM for MCF-7, and 0.17 ± 0.03 μM for MDA-MB-231 cells) was particularly promising as this complex was more selective and active than cisplatin.…”

Assessment of physiological and electrochemical effects of a repurposed zinc dithiocarbamate complex on Acinetobacter baumannii biofilms

“…ZnL1 had previously been demonstrated to have antiproliferative cytotoxic activity against TK10, UACC62 and MC7 human cancer cell lines with a IC 50 ranging from 14.28 to 22.74 µM 12 . It is not uncommon to observe that antitumoral compounds have some effect on bacterial pathogens 7 , 43 . However, experiments on animal models are needed to determine the exact range and efficacy of this compound, especially against biofilms.…”

Gold(III) Complexes Activity against Multidrug-Resistant Bacteria of Veterinary Significance

“…Considering that gold(III) complexes are well-known as cytotoxic agents, a balance between cytotoxicity and antimicrobial activity is crucial for the development of new gold(III)-based metalloantibiotics [ 11 ]. Despite many of the reported gold(III) complexes having a selectivity index in principle (that is, higher IC 50 values for the antiproliferative activity against cancer and human cells than the MIC values against bacteria), the therapeutic index usually needs to be increased by structural optimization [ 18 , 19 ].…”