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

Photodynamic Therapy of Inorganic Complexes for the Treatment of Cancer

Photodynamic therapy (PDT) is a medicinal tool that uses a photosensitiser and a light source to treat several conditions, including cancer. PDT uses reactive oxygen species (ROS) such as cytotoxic singlet oxygen 1O2 to induce cell death in cancer cells. Chemotherapy has historically utilized the cytotoxic effects of many metals, especially transition-metal complexes. However, chemotherapy is a systemic treatment so all cells in a patient\u27s body are exposed to the same cytotoxic effects. Transition metal complexes have also shown high cytotoxicity as PDT agents. PDT is a potential localized method for treating several cancer types by using inorganic complexes as photosensitizing agents. This review covers several in vitro and in vivo studies, as well as clinical trials that reported on the anti-cancer properties of inorganic pharmaceuticals used in PDT against different types of cancer

Anticancer Studies of a Cu(II) Complex in a Triple Negative Breast Cancer Cell Line

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer negative for estrogen, progesterone, and human epidermal growth factor (HER2) receptors. Hormone treatment of breast cancer involves one of the three receptors TNBC is negative for, thus leaving TNBC without an established treatment. Cisplatin is a commonly used chemotherapy in breast cancer patients, but many TNBC patients acquire cisplatin resistance. The objective is to synthesize and characterize new chemotherapeutic agents that can be used combat cisplatin resistance. Copper-containing complexes are known for inhibiting topoisomerase, breaking DNA strands, and intercalating DNA in cells. The hypothesis is treating MDA-MB-231-VIM-RFP cells with a copper(II) complex with the ligand, (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide will induce cell death with a low inhibitory concentration at 50% of cell viability (IC50 value). To test this hypothesis, we plated 15,000 cells in 96 well plates, treated MDA-MB-231-VIM-RFP cells using increasing concentrations of the copper(II) complex and incubated cells for 72 h; then utilized cell counting kit (CCK-8) cell viability assay to determine the IC50 value. The copper(II) complex had an IC50 value of 5.33 ± 0.9 μM. Flow cytometry determined time points at which cells reached apoptosis, and whether the cells activated caspase 3/7 or reactive oxygen species (ROS) after treatment. Flow cytometry showed that caspase 3/7 and ROS were activated between 22 and 33 h after treatment. It was determined that 20% of cells died before 22 h, suggesting more than one cell death mechanism. Future studies will include DNA binding studies and determining gene expression after treatment

Evaluating Anticancer Activity of a Cobalt(III) Complex with a Thiosemicarbazone Ligand Against Triple Negative Breast Cancer Cells

Cancer is one of the major causes of death in the world. Breast cancer is an uncontrolled growth of epithelial cells of the breast. Triple negative breast cancer (TNBC), a subtype of breast cancer, lacks estrogen, progesterone, and HER2 receptors. Chemotherapeutic options for TNBC which involves cisplatin have severe side effects, e.g., cytotoxicity of normal breast tissue, drug resistance, and breast cancer recurrence. The objective of this study was to determine less toxic treatment options for TNBC by using a cobalt(III) complex, which like most conventional anticancer drugs was designed to disrupt DNA synthesis as a chemotherapeutic agent. Previously, [Co(phen)2(H2O)2](NO3)3 1 (where phen = 1,10-phenanthroline) was reacted with 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) to produce [Co(phen)2(MeATSC)](NO3)3·1.5H2O·C2H5OH 2. The hypothesis is as follows: complex 2 will have a higher anticancer effect on TNBC cell line MDA-MB-231-VIM-RFP than cisplatin. In vitro cytotoxicity studies involving complex 2 with MDA-MB-231-VIM-RFP were carried out by using the Cell Counting Kit-8 (CCK-8) assay. The anti-proliferative activity of complex 2 was evaluated after incubating the drug with MDA-MB-231-VIM-RFP cells in increasing concentrations (0, 6.125, 12.5, 25, 50, and 100 μM) for 24 hours, then cell viability was measured by CCK-8 assay. Dose curves and doses required to inhibit 50% of cell growth (IC50 values) were obtained by using Origin Pro software, which revealed that MDA-MB-231-VIM-RFP cell viability was negatively impacted by complex 2 with an IC50 value of ~26 μM

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