Synthesis, Characterization, and Cytotoxicity Studies of a Copper(II) Complex with vanillin 3-ethyl-thiosemcarbazone a Ligand

Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging breast cancer subtypes to treat, as these cancer cells lack three common receptors: estrogen, progesterone, and human epidermal growth factor receptor 2. The multiple oxidation states transition metals can occupy have made this narrowly explored group popular for anti-cancer research in recent decades. Furthermore, the success of cisplatin, which has platinum as a metal center, while being a cancer-fighting agent with serious side effects, has caused other metal centers to be investigated as possible alternatives as chemotherapeutic drugs. Copper, as a biologically essential metal, makes an attractive candidate for a metal center in chemotherapeutic drugs. Additionally, metal-based compounds that contain thiosemicarbazones as ligands possess a wide range of biological activities. These ligands also have anti-cancer properties due to their ability to interfere with enzymes that catalyze DNA synthesis. Moreover, the biomedical activity of the thiosemicarbazones is enhanced by coordination to a transition metal center. Therefore, research involving thiosemicarbazones has become widespread due to their metal coordination capabilities. This study aims to synthesize, characterize, and utilize a copper(II) complex with vanillin 3-ethyl-thiosemcarbazone as a ligand in cytotoxicity studies. Elemental analysis, high resolution mass spectrometry, 1H NMR, 13C NMR, FTIR, and UV-visible spectroscopies will be utilized to characterize the complex. The cytotoxic activities of the complex will be determined using CCK-8 assay on the human TNBC cell line, MDA-MB-231-VIM RFP. Additionally, the MCF-10A human breast epithelial tissue cell line and cisplatin will be used as a controls in order to determine the efficacy of the complex

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand

In this study, 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) 1 and [Co(phen)(OCO)]Cl·6HO 2 (where phen = 1,10-phenanthroline) were synthesized. [Co(phen)(OCO)]Cl·6HO 2 was used to produce anhydrous [Co(phen)(HO)](NO)3. Subsequently, anhydrous [Co(phen)(HO)](NO)3 was reacted with MeATSC 1 to produce [Co(phen)(MeATSC)](NO)·1.5HO·CHOH 4. The ligand, MeATSC 1 and all complexes were characterized by elemental analysis, FT IR, UV-visible, and multinuclear NMR (H, C, and Co) spectroscopy, along with HRMS, and conductivity measurements, where appropriate. Interactions of MeATSC 1 and complex 4 with calf thymus DNA (ctDNA) were investigated by carrying out UV-visible spectrophotometric studies. UV-visible spectrophotometric studies revealed weak interactions between ctDNA and the analytes, MeATSC 1 and complex 4 (K = 8.1 × 10 and 1.6 × 10 M, respectively). Topoisomerase inhibition assays and cleavage studies proved that complex 4 was an efficient catalytic inhibitor of human topoisomerases I and IIα. Based upon the results obtained from the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay on 4T1-luc metastatic mammary breast cancer cells (IC = 34.4 ± 5.2 μM when compared to IC = 13.75 ± 1.08 μM for the control, cisplatin), further investigations into the molecular events initiated by exposure to complex 4 were investigated. Studies have shown that complex 4 activated both the apoptotic and autophagic signaling pathways in addition to causing dissipation of the mitochondrial membrane potential (ΔΨ). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ΔΨ, studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism

Synthesis, Characterization, and Biomedical Uses of Cobalt(III) Complexes with 1,10-Phenanthroline and Salicylaldehyde and Its Derivatives as Ligands

Triple-negative breast cancer (TNBC) presents considerable therapeutic challenges due to disease heterogeneity, absence of established therapeutic targets, and aggressive metastatic potential with higher rate of distant recurrence. In addition, TNBC is most common in younger patients (before age 40), especially in African American women, often leading to significant disease progression and poor prognosis. The limited efficacy of current treatments for advanced breast cancer has served as an impetus for a concerted effort to identify chemo-preventive agents for treatment. This process has often involved the use of cisplatin, which is widely used for the treatment of many cancers despite its high toxicity, undesirable side effects, and problems with drug resistance in primary and metastatic cancers. Biomedically relevant cobalt-containing compounds have provided promising results for cancer treatment. Novel cobalt(III)-based complexes have been synthesized and characterized in order to develop an improved treatment for TNBC with the hope that they can be used while decreasing the side effects involving the use of cisplatin. The novel complexes [Co(phen)2(salH)](PF6)2 (where phen = 1,10-phenantroline and salH = deprotonated salicylaldehyde) and [Co(phen)2(F-azo-sal)](PF6)2 (where F-azo-sal = (E)-5-((4-fluorophenyl)diazenyl)-2-hydroxybenzaldehyde) were synthesized from the starting material, anhydrous [Co(phen)2(H2O)2](NO3)3. Both complexes were characterized by elemental analysis, followed by 1H NMR and FTIR spectroscopies, and will be further characterized by high resolution mass spectroscopy (HRMS), 59Co NMR and UV-visible spectroscopies, and X-ray crystallography, where appropriate. In vitro studies will be conducted with the human TNBC cell lines, MDA-MB231 and HCC1937 to determine the IC50 values of the complexes. The human breast epithelial tissue cell line MCF-10A is the control non-cancerous cell line