In Silico Repurposing of a Novel Inhibitor (drug) of EGFR and VEGFR-2 Kinases of Cancer by Pharmacokinetics, Toxicity, Molecular Docking, and Molecular Dynamics Simulation.

Vascular endothelial growth factor is an angiogenic that promotes the development and metastasis of tumors (VEGF). The epidermal growth factor receptor, or EGFR, controls the division, growth, and death of cells via several signaling pathways. It has been found that most of the tyrosine kinase EGFR/VEGFR-2 inhibited by drugs that the FDA has approved are so far. The main objective of the present study was to identify an efficacious and selective dual inhibitor of VEGFR-2/EGFR for the treatment of cancer. Out of the 400 ligands tested against the kinases, 12 compounds demonstrated the best docking scores through molecular docking for the two kinases. Of these, only compound SCHEMBL2435814 inhibited the kinases with the highest score values when compared to a reference, vandetanib, as a dual inhibitor of EGFR/VEGFR-2 kinases through interaction with the identified active sites pocket. Following drug-likeness score toxicity and pharmacokinetic testing, the two compounds, SCHEMBL2435814 and vandetanib, were analyzed to determine how the two kinases interacted with each other. The results of calculations of π-cation interactions, hydrogen bonds, and hydrophobic interactions demonstrated a strong interaction between the two kinases and SCHEMBL2435814. Eventually, molecular dynamic modeling was used to assess the stability of complexes. This demonstrated many characteristics, including RMSF, RMSD, SASA, RG, and H-bond analysis, which demonstrated that SCHEMBL2435814 with the two kinases was more stable than vandetanib over a 100ns simulation period. By suppressing EGFR/VEGFR-2, chemical SCHEMBL2435814 may be able to postpone the signaling pathway of proteins that are essential to the advancement of cancer.

Isotope signature and elemental characteristics of subsurface formations around deep-laying coal seams probed by means of atomic and nuclear-based techniques.

A systematic investigation on the isotopic and elemental signature, for both stable and radioactive elements, and mineral contents was performed to examine the characteristics of subsurface formations collected at different depths between 3.962 km and 4.115 km around deep-laying coal seams located under the Marmarica plateau in Egypt. Concentrations of major and minor oxides (Na2O, MgO, Al2O3, SiO2, SO3, K2O, CaO, TiO2, MnO, ΣFeO + Fe2O3, SrO, ZrO2, and BaO) were determined by X-ray fluorescence and dependencies among these concentrations revealed the type and sort of the formations. Organic contents were determined by Fourier Transform infrared spectroscopy to investigate the variation of the CO/CC bonding ratio with depth. Rare earth elements (REE), specifically Y, Sc, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu were determined by inductively coupled plasma mass spectrometry while actinoids were detected by the radioactive decay of its daughter nuclei. The results showed a high trapping of REE elements and actinoids in layers above the coal seams which indicates the occurrence of aqueous flow followed by possible sorption in these layers. The mobility of the fluid was investigated using the process radioactive decay series between Ra226 and Ac228 from one side and their daughters from the other side.