Gold(III)–pyrrolidinedithiocarbamato Derivatives as Antineoplastic Agents

Abstract

Transition metals offer many possibilities in developing potent chemotherapeutic agents. They are endowed with a variety of oxidation states, allowing for the selection of their coordination numbers and geometries via the choice of proper ligands, leading to the tuning of their final biological properties. We report here on the synthesis, physico-chemical characterization, and solution behavior of two gold(III) pyrrolidinedithiocarbamates (PDT), namely [AuIIIBr2(PDT)] and [AuIIICl2(PDT)]. We found that the bromide derivative was more effective than the chloride one in inducing cell death for several cancer cell lines. [AuIIIBr2(PDT)] elicited oxidative stress with effects on the permeability transition pore, a mitochondrial channel whose opening leads to cell death. More efficient antineoplastic strategies are required for the widespread burden that is cancer. In line with this, our results indicate that [AuIIIBr2(PDT)] is a promising antineoplastic agent that targets cellular components with crucial functions for the survival of tumor cells.

Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo Biological Evaluations

“…Discussion of the FT-IR analysis is reported in the Supporting Information (Table S2). [49][50][51][52][53][54] The synthesized dipeptides P1-P5 and the corresponding gold(III) complexes IT01-IT05 were further characterizedb ym eanso fb oth mono-( 1 H, Ta ble 1) and bidimensional ([ 1 H, 13 C]HMBC, Ta ble S3) NMR analysis.…”

Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing

“…They found that the bromide derivative was more effective than the chloride one in inducing cell death for several cancer cell lines. [Au(III)Br2(PDT)] elicited oxidative stress with effects on the permeability transition pore, a mitochondrial channel whose opening leads to cell death [141]. …”

Enhanced anti-cancer activities of a gold(III) pyrrolidinedithiocarbamato complex incorporated in a biodegradable metal-organic framework

“…[28]. Taken all the results of this work together, we reckon that ZnBTCA could protect the relatively reactive gold(III) complex 1 against hydrolysis/ reduction in culture medium and thus yielded preferential cytotoxic activities towards the A2780cis cells.…”

“…Unlike the clinically-used platinum (II) drugs which target DNA to execute their cytotoxic activities, many gold(III) dithiocarbamato complexes were found capable to induce cancer apoptotic cell death via inhibition of thioredoxin redox system and proteasomes, and activation of ERK pathway [22][23][24][25]. Various peptidomimetic gold(III) dithiocarbamato complexes show enhancing anti-cancer activities and cancer-cell selectivity in vitro [26,27] [28]. These complexes were found to undergo extensive hydrolysis in aqueous medium, which in turn affects their cytotoxic activities against the cancer cells.…”

“…By means of 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium bromide (MTT) assays [46], the in vitro cytotoxicity of 1 was evaluated using cancerous cell lines of human A recent study has shown that 1 exhibits a rapid (three-hour) dose-dependent cytotoxic activity towards some human cancer cell lines including the highly aggressive osteosarcoma (SAOS-2) and colorectal carcinoma (HCT116) [28].…”