Investigations of Ni(II)Cysteine-Tyrosine Dithiocarbamate Complex: Synthesis, Characterization, Molecular Docking, Molecular Dynamic, and Anticancer Activity on MCF-7 Breast Cancer Cell Line.

OBJECTIVE: Breast cancer ranks second in terms of the highest number of cancer deaths for women worldwide and is one of the leading causes of death from cancer in women. The drug that is often used for chemotherapy is cisplatin. However, cisplatin drugs have a number of problems, including lack of selectivity, unwanted side effects, resistance, and toxicity in the body. In this work, we investigated Ni(II) cysteine-tyrosine dithiocarbamate complex against breast cancer. METHODS: Research on the new complex compound Ni(II) cysteine-tyrosine dithiocarbamate have several stages including synthesis, characterization, in-silico and in-vitro testing of MCF-7 cells for anticancer drugs. The synthesis involved reacting cysteine, CS2, KOH and tyrosine with Mn metal. The new complex compound Ni(II) cysteine-tyrosine dithiocarbamate has been synthesized, characterized, and tested in vitro MCF-7 cells for anticancer drugs. Characterization tests such as melting point, conductivity, SEM-EDS, UV Vis, XRD, and FT-IR spectroscopy have been carried out. RESULT: The synthesis yielded a 60,16%, conversion with a melting point of 216-218 oC and a conductivity value of 0.4 mS/cm. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting at a sample concentration of 250 µg/mL and an IC50 value of 618.40 µg/mL. Molecular docking study of Ni(II) cysteine-tyrosine dithiocarbamate complex identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α showing active site with acidic residue amino E323, M388, L387, G390 and I389. Hydrophobic and hydrophobic bonds are seen in Ni(II) cysteine-tyrosine dithiocarbamate - Estrogen α has a binding energy of -80.9429 kJ /mol. CONCLUSION: there were 5 residues responsible for maintaining the ligand binding stable. The compound had significant Hbond contact intensity, however, it was not strong enough to make a significant anticancer effect. Though the synthesized compound shows low bioactivity, this research is expected to give valuable insight into the effect of molecular structure on anticancer activity.

Novel Complex of Zinc (II) Dichloroethylenediamine: Synthesis, Characterization, In-silico, and In-vitro Evaluation against Cervical Cancer Cells.

OBJECTIVE: Cervical cancer is a malignancy originating from the cervix and often caused by oncogenic Human Papilloma Virus (HPV), specifically subtypes 16 and 18. Anticancer drugs are chemotherapeutic compounds used for cancer treatment. Therefore, this research aims to synthesize and characterize Zinc (II) dichloroethylenediamine (Zn(en)Cl2) complex, as well as determine its antiproliferative activity against HeLa cells. The Zn(en)Cl2 complex was successfully synthesized, and the antiproliferative activity was tested. METHODS: The synthesis involved reacting ethylenediamine and KCl with Zn metal. The complex formed was characterized using a conductometer, UV-Vis spectroscopy, FT-IR spectroscopy, and XRD, while the activity was measured against HeLa cells. RESULT: The synthesis yielded a 56.12% conversion with a melting point of 198-200 oC and a conductivity value of 2.02 mS/cm. The Zn(en)Cl2 complex showed potential activity against HeLa cells with an IC50 value of 898.35 µg/mL, which was evidenced by changes in the morphological structure of HeLa cells. Its interaction with DNA targets was investigated by employing molecular docking. CONCLUSION: The observed data indicated that the Zn(en)Cl2 complex bound to DNA at the nitrogenous base Guanine (DG) by coordinate covalent bonds. Interestingly, DG maintained interaction with the complex until the end of the docking simulation. Additionally, molecular dynamics (MD) simulation was conducted, and the results showed that Zn(en)Cl2 remained bound to the DNA binding pocket all through the process.

Design anticancer potential of Zn(II)isoleucinedithiocarbamate complex on MCF-7 cell lines: synthesis, characterization, molecular docking, molecular dynamic, ADMET, and in-vitro studies.

Cisplatin is a cancer medication widely used today, but it still poses some problems due to its toxic properties in the body. To overcome this issue, a new complex has been developed as a potential anticancer drug prospect by minimizing its toxic consequences. A novel Zn(II)IleDTC complex containing isoleucine dithiocarbamate ligands has been produced and analyzed using a range of analytical and spectroscopic methods. The Zn(II) IleDTC complex were characterized using various methods, including UV-Vis spectroscopy, FT-IR, determination of melting point, conductivity, and HOMO-LUMO analysis. Furthermore, computational NMR spectrum analysis was conducted in this study. Molecular docking studies was conducted to evaluate the potential of Zn(II) isoleucine dithiocarbamate as an HIF1 inhibitor. The results showed that the Zn complex exhibited a good docking score of -6.6 and formed hydrogen bonds with ARG 17, VAL264, and GLU15, alkyl bonds with TRP27 and LEU32, and Pi-Alkyl bonds with PRO41 and ARG44. This suggests that the Zn(II) isoleucine dithiocarbamate complex could be a promising candidate for cancer treatment with potential HIF1 inhibition properties. To assess the dynamic stability and efficacy of protein-ligand interactions over time, molecular dynamics simulations was conducted for both individual proteins and protein complexes. The cytotoxicity evaluation of Zn(II) isoleucine dithiocarbamate against MCF-7 cells obtained an IC50 value of 362.70 µg/mL indicating moderate cytotoxicity and morphological changes of cancer cells causing cancer cells to undergo apoptosis. The Zn(II) isoleucine dithiocarbamate complex may have promising potential as an anticancer compound due to its significant inhibitory effect on the breast cancer cell line (MCF7). According to the ADMET study, the complex exhibits drug-like characteristics with low toxicity, further supporting its potential as a viable drug candidate.

The new potential application for Mg(II) cysteinedithiocarbamate complex with anticancer activity.

OBJECTIVE: The new Mg(II) cysteindithiocarbamate complex drug has been synthesized by the in-situ method and tested for its anticancer activity in vitro. METHOD: Mg(II) cysteindithiocarbamate complexes were characterized using Ultra Violet Visible, Infra-Red, melting points, and molar conductivity. RESULTS: The UV-Vis data of cysteindithiocarbamate Mg(II), shows that at 296 nm and 385 nm was occurred the electronic transitions π → π* and n → π* for CS2 and N =C =S. Whereas the IR data at wavelengths in the 393-540 cm-1 shows that there has coordinated between Mg(II) with Sulfur (S), Nitrogen (N), and Oxygen (O) atoms from cysteinedithiocarbamate ligands. CONCLUSION: The cytotoxicity test results showed that the Mg complex's cytotoxicity was higher than that of the cytotoxicity of the Mg metal without ligands, which means that the Mg complex can be developed as a potential new anticancer drug.

Synthesis, characterization, molecular docking studies of Mn(II)Prolinedithiocarbamate and its potential as anticancer agents.

Breast cancer is a non-communicable disease but dangerous for women, and research on anti-breast cancer drug compounds is being investigated. Mn(II)Prolinedithiocarbamate (MnProDtc) complex was synthesized and characterized in cytotoxicity and in silico assay by molecular docking. Dithiocarbamate ligand plays an important role as an anticancer agent. Melting point determination, conductivity, UV-Vis spectroscopy, FT-IR spectroscopy, XRD, and HOMO-LUMO have been studied. The binding of MnProDtc to cancer cells was examined by molecular docking, showing that the active sites of the MCF-7 strain, namely the protein O(6)-methylguanine-DNA methyltransferase (MGMT), caspase-8, and the estrogen receptor, bind to the complex. The results of the cytotoxic test of MCF-7 cancer cells undergoing apoptosis at a concentration of 37.50 µg/ml with an IC50 value of 453.96 µg/ml showed moderate anticancer activity in MCF-7 cancer cells.

Anticancer potential of Cu(II)prolinedithiocarbamate complex: design, synthesis, spectroscopy, molecular docking, molecular dynamic, ADMET, and in-vitro studies.

Breast cancer continues to be a major health issue for women all over the world. Cancer medications like cisplatin, which are widely used, still have negative side effects. The novel complex was created as a potential anticancer medication candidate that is both effective and safe, with few side effects. The Cu(II) complex using the prolinedithiocarbamate ligands was synthesized in situ. The Cu(II) complexes Characterization by UV-Vis, FT-IR spectroscopy and melting point determination, conductivity, and HOMO-LUMO were studied. Computational NMR spectrum analysis was performed. The interaction of Cu(II)prolineditiocarbamate complex with cancer cell target protein (MCF-7) was confirmed by molecular docking and molecular dynamic. The pharmacokinetic/ADMET properties were also performed on the complex. Results of the cytotoxic complex test against cancer cells (MCF-7) undergoing apoptosis with an IC50 value of 13.64 µg/mL showed high anticancer activity in MCF-7 cancer cells. The in-vivo data for Cu(II)prolineditiocarbamate complex was predicted using the Protox online tool with an LD50 value of 2500 mg/kg and belonging to the GHS toxicity class 5, which means the compound has a low acute toxicity effect. The Cu(II) prolineitiocarbamate complex may pave the way for the development of essential metal-based chemotherapy for the treatment of breast cancer.Communicated by Ramaswamy H. Sarma.

A New Complex Design of Fe (II) Isoleucine Dithiocarbamate as a Novel Anticancer and Antivirus against SARSCOV-2 (COVID-19).

BACKGROUND: This study was carried out to synthesize a new complex of Fe(II) with isoleucine dithiocarbamate ligand and to determine its potential as an anticancer and antiviral agent for SARSCOV-2. METHODS: The synthesized complexes were then characterized by UV-vis and FT-IR spectroscopy and their melting points. The value of the conductivity of the complex compound is also determined. Anti-cancer activity was tested in vitro and molecular docking. Its potential as an antiviral against SARSCOV-2 was also carried out by molecular docking. Pharmacokinetics/ADMET properties were also carried out on the complex. RESULT: Spectral results showed the successful synthesis of Fe(II) isoleucine dithiocarbamate complex. The complex produced UV-vis spectra at 268 and 575 nm, and the IR data at 399-599 cm-1 showed the coordination between the Fe(II) atoms with sulphur, nitrogen and oxygen of the isoleucine dithiocarbamate ligand. Fe(II) isoleucine dithiocarbamate had a cytotoxicity effect on the MCF-7 cell line (IC50 =613 µg/mL). The complex significantly caused morphological changes in the breast cancer cell line, finally leading to cell apoptosis. CONCLUSION: Cytotoxic test of Fe(II) isoleucine dithiocarbamate showed moderate anticancer activity on MCF-7 cancer cells and showed antiviral activity against SARSCOV-2 by interfering with spike glycoprotein -ACE2 receptors, and inhibiting major proteases and 3Clpro.

Analysis of antioxidant activity on cocktail honey products as female pre-conception supplements.

OBJECTIVE: Cocktail honey is derived from a mixture of honey (trigona sp.), bee bread, and homogeneous royal jelly. The material has a phenolic content rich in antioxidants that are beneficial for women's reproductive health, especially for pre-conception, because it can suppress the content of free radicals in the body. Antioxidants are useful to overcome oxidative damage due to free radicals in the body that prevent various diseases from increasing fertility during pre-conception. METHOD: This study used the DPPH (2,2-diphenyl-1-picrylhydrazyl) test method using UV-vis spectrophotometry to express the value of free radical reduction activity as IC50 (inhibitory concentration) values. RESULTS: The DPPH test on cocktail honey products obtained an average yield of 4577.7µg/mL, which was included in the product category was very weak in the antioxidant activity content. CONCLUSION: The content contained in the honey cocktail contains weak bioactive content by assessing the antioxidant content using DPPH. The difference in the results of antioxidant activity tests using DPPH is caused by the test method and the conditions used in processing, homogeneous ingredients, solvent volume, extraction time, temperature, and pressure in product management.

Ginger honey affects cortisol, estrogen and glutathione levels; preliminary study to target preconceptional women.

OBJECTIVE: This study was aimed to determine the effect of ginger honey supplementation on cortisol, glutathione, and estrogen levels. The study was conducted on mice that had not yet experienced conception, and prior stress induction was carried out so that they could be continued for human trials at the preconception stage and subjects who experienced mild stress. METHOD: It was an in vivo study, pretest-posttest control group design. The sample of this study was 2-3 months female Balb/c mice, divided into negative control and ginger honey intervention as much as 28mg/20g BW for 14 days-the ELISA method used to examine cortisol hormone, glutathione levels, and estrogen levels. The mice chosen were those that had never experienced conception, and before the intervention, swimming activities were carried out on the mice until they showed symptoms of stress. RESULTS: Results show 42mg/20g BW of ginger honey administration for 14 days increased 1.892 ng/dl of cortisol (p = 0.165), increased 2.438 ng/dl of glutathione (p=0.002), and also increased 22.754ng/ml estrogen levels in induced stress Balb/c female mice (p=0.001). CONCLUSION: Ginger honey did not affect reducing cortisol levels but increasing glutathione and estrogen levels significantly. Ginger honey supplements are the potential to use as complementary therapies.

The comparison of Zn(II) arginine dithiocarbamate cytotoxicity in T47D breast cancer and fibroblast cells.

BACKGROUND: With essential metals being studied and developed as anticancer agents, this study aims to explore the anticancer activity of Zn(II) arginine dithiocarbamate in the T47D and fibroblast cell lines. METHOD: The Zn(II) arginine dithiocarbamate complex was prepared by the in situ method and characterized using infra-red spectroscopy, melting point, X-ray fluorescence, and X-ray diffraction instruments. The complex compound was tested for its cytotoxicity to the T47D breast cancer and fibroblast cell lines. RESULTS: The cytotoxicity of the Zn(II) arginine dithiocarbamate complex to the T47D breast cancer cell line obtained IC50 = 3.16 µg/mL, while cisplatin obtained IC50 = 28.18 µg/mL. The cytotoxicity of the Zn(II) arginine dithiocarbamate complex to fibroblast cells obtained IC50 = 8709.63 µg/mL. CONCLUSION: The Zn(II) arginine dithiocarbamate complex has increased active cytotoxicity compared to cisplatin in inducing morphological changes in the T47D breast cancer cell line and is relatively non-toxic to fibroblast cells.

Potential anticancer activity of Mn (II) complexes containing arginine dithiocarbamate ligand on MCF-7 breast cancer cell lines.

INTRODUCTION: Cancer refer to genetic changes in the DNA structure accompanied by abnormal growth of normal cells, and resulting in the death of these structures, and is a disease currently recognized as a major cause of mortality globally. Chemotherapy plays important role in breast cancer management. Non-toxic metals have been developed to replace the highly toxic cisplatin, an example being Manganese. Furthermore, Ligands have displayed great capabilities in the determination of anticancer properties, and an essential agent exploited in drug development is arginine dithiocarbamate. Therefore, this study was conducted to examine the anticancer potentials of Mn (II) arginine dithiocarbamate. METHODS: The synthesis and spectroscopic analysis of the Mn (II) Arginine dithiocarbamate complex was successfully carried out. Then, the complexes were characterized through the employment of the UV-Vis, FT-IR, as well as the melting point tests, and subsequently analyzed for anticancer activities through in vitro means. The compound was produced from UV-Vis spectrum at 246 and 385 nm wavelengths and IR spectrum at wave numbers 354-499 cm-1. RESULTS: The results revealed the cytotoxicity of Mn (II) Arginine dithiocarbamate against the MCF-7 cell line, observed from a significant change in the morphology of the cancer cells with IC50 value of 211.53 µg/mL. CONCLUSION: The compound, Mn (II) Arginine dithiocarbamate has effective anticancer potentials against MCF-7 cancer cells.