Dithiocarbazate–Fe^III, −Co^III, −Ni^II, and −Zn^II Complexes: Design, Synthesis, Structure, and Anticancer Evaluation

Abstract

Non-platinum-metal complexes show great potential as anticancer agents. Herein, a series of dithiocarbazate non-Pt-metal complexes, including [FeIII(L)2]·Cl·2H2O 1, [CoIII(L)2]·NO3·2.5H2O 2, [NiII(L)2] 3, and [ZnII(L)2] 4, have been designed and evaluated for their efficacy as antineoplastic agents. Among them, complex 2 exhibited higher anticancer efficacy than complexes 1, 3, 4, and cisplatin against several cancer cell lines. Hemolysis assays revealed that complex 2 showed comparable hemolysis with cisplatin. In vivo anticancer evaluations showed that complex 2 could retard tumor xenograft growth effectively with low systemic toxicity. Further studies revealed that complex 2 suppressed cancer cells by triggering multiple mechanisms involving the simultaneous inhibition of mitochondria and glycolytic bioenergetics. Overall, our study provides new insights into the anticancer mechanism of Co complexes, which can be used as a good strategy to overcome the flexibility of cancer cells to chemotherapy adaptation.

Designing a multitarget In(iii) compound to overcome the resistance of lung cancer cells to cisplatin

“…Non-Pt metal compounds have been proposed as promising anticancer drugs to overcome cisplatin resistance. 41,42 On the basis of the properties of In( iii ) and thiosemicarbazones, In( iii ) 2-acetylpyridine thiosemicarbazone compounds were synthesized, and their anticancer activities were investigated (Table 1). The obtained results demonstrated that In( iii ) compounds exhibit remarkable anticancer activity.…”

Developing a Ruthenium(III) Complex to Trigger Gasdermin E-Mediated Pyroptosis and an Immune Response Based on Decitabine and Liposomes: Targeting Inhibition of Gastric Tumor Growth and Metastasis

“…Although platinum (Pt) drugs are considered to be the first-line chemotherapeutics in the clinic against various solid tumors, DNA-targeted Pt-based anticancer drugs not only have severe side effects and a lack of targeting but also are ineffective in inhibiting tumor metastasis. − At present, to overcome the shortcomings of Pt drugs, one of the most promising strategy is to design non-Pt metal drugs based on other new anticancer mechanism(s) and then use carriers to improve their targeting ability and reduce their side effects in vivo . − …”

A Series of Non-Oxido VIVComplexes of Dibasic ONS Donor Ligands: Solution Stability, Chemical Transformations, Protein Interactions, and Antiproliferative Activity

“…Over the last years, the interest in the study of ONS donor ligands has increased significantly due to their ligation properties and potential applications of their transition metal complexes in pharmacology and medicine. ,− For example, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, well known as triapine, is one of the most extensively studied drugs and has been tested in nearly 30 clinical phases I/II trials as an antiproliferative agent . Likewise, di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC-TSC) has also entered clinical phase I studies as a chemotherapeutic agent. , Out of this class of compounds, similar to thiosemicarbazones, S-substituted dithiocarbazates (DTCs) are also well known for their antitumor, antimicrobial, antifungal, and antibacterial activities. ,− ,,, Moreover, N ’-(phenyl-pyridin-2-yl-methylene)-hydrazine carbodithioic acid methyl ester (PHCM) was also found to enhance radiation-induced cell death of an NSCLC cell line, H460, both in vivo and in vitro . Interestingly, the possible use in bio-imaging and in the treatment of pancreatic cancer of a dithiocarbazate-copper complex has been recently published …”