Discovery of 1,2,4-triazine dithiocarbamate derivatives as NEDDylation agonists to inhibit gastric cancers

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms

“…Because of their remarkable reactivity and broad applicability as precursors and intermediates in chemical synthesis, organic dithiocarbamates have attracted much interest as enzyme inhibitors and have a significant impact on biology. [152][153][154][155][156] Additionally, they have been utilized in the treatment of bacterial and fungal infections, HIV and cancer. [157][158][159] As a result of the chelate effect, dtc-ligands form quite stable complexes with transition metals, which prevents…”

“…In one example, laboratory trials of gold(III) dithiocarbamate complexes were found to be identical to or higher than that of cisplatin in vitro. 150,151,154,155,157 Bidentate ligands, such as DTC's, generate metal complexes that are quite stable due to chelate effect where breakdown and subsequent loss of the dithiocarbamato ligand do not occur.…”

Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities

“…Dithiocarbamates are an important class of sulfur-containing organic compounds with a wide range of applications in both academia and industry [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. They serve as fungicides and pesticides in agriculture [ 17 , 18 , 19 ], vulcanization agents in the rubber industry [ 20 ], radical chain transfer agents in polymerization [ 21 ], effective ligands in coordination chemistry [ 22 ], and, last but not least, as biologically important structural motifs in medicinal chemistry ( Scheme 2 ) [ 23 , 24 , 25 , 26 , 27 ].…”

“…Covalently combining two known pharmacophores yields a novel hybrid molecule, which can possess integrated advantages for optimizing certain biological activities and overcoming the deficiencies of a single drug [ 32 , 33 , 34 , 35 ]. In view of the high performance of dithiocarbamate derivatives in structural modification, the synthesis of OA-dithiocarbamate conjugates may enhance the polarities and antitumor properties of the reaction products in a readily accessible manner [ 7 , 23 , 24 , 25 , 26 , 27 ]. The structural modifications of OA have mainly focused on the C-3 hydroxyl and C-28 carboxyl groups ( Scheme 1 ) [ 7 ].…”

Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity

“…Our group reported a novel tertiary amide derivative 6 as the NEDDylation activator to inhibit tumour progression in vitro and in vivo 11 . Compound 7 targeting NEDDylation displayed the potent activity MGC-803, EC-109, and PC-3 cells with IC 50 values of 2.35, 10.1, and 5.71 μM 12 . All these findings showed that NEDDylation modulators might be potential anticancer agents.…”