New oxomethacrylate and acetamide: synthesis, characterization, and their computational approaches: molecular docking, molecular dynamics, and ADME analyses.

The compounds 2-chloro-N-(3-methoxyphenyl)acetamide (m-acetamide) and 2-(3-methoxyphenylamino)-2-oxoethyl methacrylate (3MPAEMA) were synthesized in this study for the first time in the literature. FTIR, 1H, and 13C NMR spectroscopic techniques were used to characterize it. Subsequently, computational techniques were used to assess various ADME factors, such as drug-likeness properties, bioavailability score, and adherence to Lipinski's rule. Finally, molecular docking experiments were conducted with the human topoisomerase α2 (TOP2A) protein to verify and validate the reliability and stability of the docking procedure. The results of the docking scores, which quantify binding affinity, indicated that these derivatives exhibited a stronger affinity for TOP2A.

Evaluation of the effect of cannabidiol on the THLE-2 liver cell line exposed to lead.

Environmental and soil pollution increase the likelihood of human exposure to toxic metals. Therefore, there is a need for new methods and substances to protect individuals against the harmful effects caused by toxic metals. The study is the first to aim at determining the protective effect of cannabidiol (CBD) against oxidative stress and inflammation induced by toxic metal exposure in Transformed Human Liver Epithelial-2 (THLE-2) cell lines representing healthy liver cells. The IC50 value was determined by exposing THLE-2 human liver healthy cell line to different molarities of lead (Pb) using the XTT kit. The protective efficacy of CBD was assessed by adding 5 µM CBD in addition to the Pb doses determined at IC50 levels to the Pb groups created in cell lines. The levels of GSH, MDA, MPO, CAT, TNF-α, IL-1ß, and IL-6 in cell lines were determined using ELISA kits. The inhibition of toxic metal entry into the cells by CBD was assessed through ICP-MS analysis. The IC50 value for Pb was determined as 10 µM in 2D cell lines and 25 µM in 3D cell lines. It was observed that the application of 5 µM concentration of CBD, along with the determined IC50 doses for Pb, increased the cell proliferation rate. Furthermore, the decrease in GSH and CAT levels and the increase in MDA, MPO, TNF-α, IL-1ß, and IL-6 levels observed in cell lines treated only with Pb were reversed with the application of CBD. The ICP-MS analysis revealed that CBD reduced the cellular uptake of Pb. The reversal of oxidative stress and inflammation induced by Pb, the increase in cell proliferation, and the reduction in the cellular uptake of toxic metals by CBD can be considered as strong evidence for the protective use of CBD in Pb exposures.

The Determination of Molecular and Toxicological Mechanisms of Cucurbitacin E in Model Organism Drosophila melanogaster and Various Cancer Cell Lines: Molecular Modelling, Docking and Dynamic Simulation Studies.

INTRODUCTION: Cucurbitacins are one of the most important components of Ecballium elaterium. Among the cucurbitacins, Cucurbitacin E was the first to be isolated. This study focused on screening the anticancer and insecticidal potential of Cucurbitacin E by the in-vitro, invivo, and in-silico methods. METHODS: In the study, toxicity analysis of Cucurbitacin E was determined on HeLa, Caco 2 cancer cell lines and D. melanogaster. While the expression levels of the BAD, BCL-2, AKT-1 and H-purine genes of cancer cell lines were determined, the CG15530, BUFFY, AKT-1 and Purine genes of D. melanogaster were determined by RT-PCR. Besides, molecular docking and dynamic properties of Cucurbitacin E with human and insectoid enzymes were presented in silico. RESULTS: The IC50 value of Cucurbitacin E in the HeLa ovarian and Caco 2 colon cancer cell lines was determined to be 42 ug/ml and 85 ug/ml, respectively. The LC50 and LC99 doses for fruit flies were determined to be 47,693 µg/ml and 133,251 µg/ml, respectively. Gene expression analysis revealed that Cucurbitacin E showed the greatest effect on Purine and AKT-1 genes in D. melanogaster. We analyzed all genes by Western blot but did not detect significant changes in genes other than H-purine. In silico studies revealed that the Purine protein of D. melanogaster had the highest bonding energy with Cucurbitacin E as a ligand. Similarly, Cucurbitacin E showed great affinity towards H-purine (-10.2 kcal/mol). Molecular dynamics simulation studies were also performed to determine the stability of the dynamic process. CONCLUSION: As a result of our in vivo, in vitro and bioinformatic analyzes, it has been seen that Cucurbitacin E is effective against the cancer types and model insects studied.

In vivo, in vitro and Molecular Modelling Analysis of Isoquercetin, Roseoside, Coreximine, Anonaine, and Arianacin Molecules.

INTRODUCTION: Annona muricata is a member of the Annonaceae family. This plant has a high concentration of acetogenin, which gives it excellent therapeutic property. Researchers have tested this miraculous herb in breast cancer cells treatment and observed that it could be a source of anti-cancer agents. The proposed study focused on screening the anticancer biological activity of Annona muricata plant by using the in vitro, in vivo, and in silico methods. METHODS: In in vitro analysis, the IC50 was determined on two-dimensional and three-dimensional breast cancer cells. 2D cells were cultured on flat dishes typically made of plastic, while 3D cells were cultured using the hanging drop method. In in vivo analysis, Drosophila melanogaster was preferred, and the LC50 was determined. In in silico analysis, molecular docking studies have been carried out on the different classes of Annona muricata acetogenins against the target proteins. Nearly, five acetogenins were selected from the literature, and docking was performed against human Bcl-2, Bad and Akt-1 proteins. RESULTS: In vitro and in vivo results revealed the IC50 value of 2D MDA-MB-231 cells as 330 µg.mℓ-1, of 2D MCF-7 cells as290 µg.mℓ-1, and of 3D MCF-7 and MDA-MB-231 cells about 0.005 g.mℓ-1; the LC50 value of Drosophila melanogaster was determined as 0.1 g.mℓ-1. In silico results revealed that the docked complex formed by Isoquercetin showed better binding affinity towards target proteins. CONCLUSION: As a result of the analysis, the Annona muricata plant has been observed to be effective against cancer and likely to be a potential drug.

The molecular interaction of human anti-apoptotic proteins and in silico ADMET, drug-likeness and toxicity computation of N-cyclohexylmethacrylamide.

Cancer is an uncontrolled growth of normal cells and apoptosis has an important role in cancer progression and cancer treatment. Antiapoptotic proteins are overexpressed in several tumors including breast, brain, lung cancer cells. The protein-ligand interaction has a critical role in drug designing. The present study aims to evaluate the interaction of synthesized N-cyclohexylmethacrylamide (NCMA) with proteins using in silico molecular docking and toxicity analyses. The NCMA monomer was synthesized and characterized by our team, previously. Kinetics stability, binding affinities and toxic potential of protein-NCMA complex were examined with the aid of molecular simulation. The toxicity results of this study indicate that NCMA is a sample with low toxic potential. According to the docking results, NCMA may be a drug active substance with chemical modifications and toxicity results support this situation. The drug-likeness and ADMET parameters were screened properties of NCMA.

Synthesis, Characterization, Biological Evaluation and Molecular Docking Studies of New Oxoacrylate and Acetamide on HeLa Cancer Cell Lines.

BACKGROUND: In recent years, the discovery and development of new drugs play a critical role in cancer therapy. OBJECTIVE: In this study, the effect of MPAEA and p-acetamide on cellular toxicity and on silico in HeLa cancer cells have been investigated. METHODS: In this study, 2-choloro-N-(4-methoxyphenyl)acetamide (p-acetamide) and 2-(4- methoxyphenylamino)-2-oxoethyl acrylate (MPAEA) have been synthesized and characterized by FTIR, 1H, and 13C-NMR. Cytotoxicity of p-acetamide and MPAEA have been investigated by XTT cell proliferation assay on the HeLa cell line. IC50 values of p-acetamide and MPAEA have been identified on the HeLa cell line. Further, a molecular docking study was carried out by Autodock Vina using BCL-2 (PDB ID: 4MAN), BCL-W (PDB ID: 2Y6W), MCl-1 (PDB ID: 5FDO) AKT (PDB ID: 4GV1) and BRAF (PDB ID: 5VAM) as a possible apoptotic target for anticancer activity. RESULTS: According to the obtained results, MPAEA and p-acetamide were successfully synthesized and characterized. The interactions between ligands and anti-apoptotic proteins were evaluated by molecular docking, and their free energy of binding was calculated and used as a descriptor. CONCLUSION: In vitro and in silico, the results demonstrated that MPAEA had potent anticancer activity on the HeLa cell line.

Sequence variants of CYP345a1 and CYP6a14 gene regions in Tribolium castaneum (Coleoptera: Tenebrionidae) adults treated with the novel characterized Bolanthus turcicus (Caryophyllaceae) extract.

In this study, various doses of plant extracts that obtained from Bolanthus turcicus was applied to an important storage pest Tribolium castaneum adults. Bolanthus turcicus is an endemic species and spreads on the Hasan Mountain above Karkin town (Turkey, Aksaray province). The plant species was collected from June to July with the field study to be carried out in this region. Obtained extract of plant was analyzed by gas chromatography mass spectrometry (GC-MS) method. The doses were defined during the study and the concentrations that kill 50% and 99% of the population were determined after applications. After 24 h, DNA was isolated from live and dead individuals that obtained from LC50 and LC99 concentration applications and analyzed for Cytochrome P450-mediated detoxification resistance genes, CYP345A1 and CYP6A14 gene regions, by polymerase chain reaction (PCR). CYP genes in insects are known to be rapidly regulated when exposed to insecticides. In the study, in order to screen for 206 bp and 353 bp fragments of CYP345A1 and CYP6A14 genes in T. castaneum adults were amplified using specific primers, respectively. DNA direct sequencing was performed on each template using the forward primer. When compared to the control, it is believed that mutation differences in live and dead individuals according to the sequencing results obtained from survival and dead adults, may allow these genes to play a protective role against the toxic effect of B. turcicus extract.