Anticancer Activity and Apoptosis Induction of Gold(III) Complexes Containing 2,2′-Bipyridine-3,3′-dicarboxylic Acid and Dithiocarbamates

Abstract

Three novel gold(III) complexes (1–3) of general composition [Au(Bipydc)(S2CNR2)]Cl2 (Bipydc = 2,2′-bipyridine-3,3′-dicarboxylic acid and R = methyl for dimethyldithiocarbamate (DMDTC), ethyl for diethyldithiocarbamate (DEDTC), and benzyl for dibenzyldithiocarbamate (DBDTC)) have been synthesized and characterized by elemental analysis, FTIR and NMR spectroscopic techniques. The spectral results confirmed the presence of both the Bipydc and dithiocarbamate ligands in the complexes. The in vitro cytotoxic studies demonstrated that compounds 1–3 were highly cytotoxic to A549, HeLa, MDA-231, and MCF-7 cancer cells with activities much higher (about 25-fold) than cisplatin. In order to know the possible mode of cell death complex 2, [Au(Bipydc)(DEDTC)]Cl2 was further tested for induction of apoptosis towards the MCF-7 cells. The results indicated that complex 2 induces cell death through apoptosis.

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

“…The best complex 333 , which contained ethyl for diethyldithiocarbamate (DEDTC) in the MCF-7 cell line, reached 2.7 ± 0.1 μM, and further studies showed that complex 333 induced cell death through apoptosis. 239 Babak et al designed a range of new gold( iii ) complexes, and activated and released metformin prodrug by adjusting the cyclometalated gold( iii ) complex. The cytotoxicity of complex 334 was the most effective among them.…”

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

“…Furthermore, dithiocarbamates have the potential to activate key proteins involved in cellular mechanisms such as apoptosis, oxidative stress, transcription, and degradation, which now has sparked interest in these molecules as chemotherapeutic agents. 71,171,174,200 As mentioned above, studies on cancer cells have indicated that cancerous cells are far more susceptible to proteosome suppression than normal cells. 201–205 This opens opportunities to design compounds which preferentially bind to proteasomes.…”

“…Furthermore, due to the interaction of an extra S-donor moiety such as cysteine, methionine, and other amino acids with S-groups, square planar complexes from dithiocarbamate ligands could result to even more stable complexes. [174][175][176] As a result, further complexation of the central metal with protein molecules containing the thiol moiety which is likely to cause severe side effects, such as liver toxicity (hepatotoxicity) and kidney toxicity (nephrotoxicity) are prevented. [177][178][179][180] Metal complexes from dithiocarbamate nanoparticles and polymeric materials are increasingly being explored as therapeutic strategies.…”

Serum-Stable Gold(III) Bisphosphine Complex Induces Mild Mitochondrial Uncoupling and In Vivo Antitumor Potency in Triple Negative Breast Cancer

“…Several cyclometalated Au­(III) complexes have been shown to induce significant antiproliferative activity by apoptosis or autophagy. − We expected that Au-1 – Au-5 recapitulate these features. Au-1 – Au-5 showed lower IC 50 values compared to cisplatin (a first-line chemotherapeutic drug) in the panel of cancer cells studied: MDA-MB-468 and MDA-MB-231 (human breast cancer), 4T1 (murine breast cancer), and BT333 (human glioblastoma) 72 h post-treatment by MTT (Table , Figures S60–S65).…”