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Context: Electronic sustainable behavior on the material surface and in situ metal configuration were accompted with some metal atoms like Li, Na, and K elements. Metal-doped ZrO2 crystal exported modified characteristics related to electronic conduction and exhibited some dynamic modification around the surface of the metal oxide. Computational perturbations were considered to discuss the modification behavior in addition to the studied Li, Na, and K metals. Optimization of the three doping systems was achieved followed by generating DOS and electronic band structure maps. A dynamic simulation was performed with temperature over 2000 k: the presence of the metal on the surface and prediction of its ZrO2 inclusion leading to access adsorption behavior, besides generating predictive designed models described the adsorption affinity on the solid-state surface. It cannot be neglected the importance of various metals as a main role in chemotherapy. Molecular docking investigation was considered to predict the binding behavior of the studied metal ZrO2 carrier system as an anticancer agent. Also, docking affinity was helpful in comparing the active sites binding for the studied metals, resulting in a notable binding affinity for both Li- and Na-zirconia incorporation. Methods: The program PWSCF, which is a component of the quantum ESPRESSO suite for quantum simulation of materials, was used to construct geometric systems. The generalized gradient approximation in the Perdew-Burke-Ernzerhof (GGA/PBE) function with D3 correction (Becke-Jonson damping) was applied to the exchange-correlation energy. As the last step in the DFT postulation and design, adsorption locator annealing was carried out on the convergent models using the Materials Studio simulation package. The main roles played by metal atoms are in protein binding and the suppression of bio-active regions. For the docking process, the protein was produced using AutoDock 4.2 and Discovery Studio software in accordance with the usual methodology. Chimera and Discovery Studio were used to examine the docking data that was processed after generating specific grid box dimensions for 7BTN. [ABSTRACT FROM AUTHOR]

High-risk neuroblastoma is an aggressive childhood cancer that is characterized by high rates of chemoresistance and frequent metastatic relapse. A number of studies have characterized the genetic and epigenetic landscape of neuroblastoma, but due to a generally low mutational burden and paucity of actionable mutations, there are few options for applying a comprehensive personalized medicine approach through the use of targeted therapies. Therefore, the use of multi-agent chemotherapy remains the current standard of care for neuroblastoma, which also conceptually limits the opportunities for developing an effective and widely applicable personalized medicine approach for this disease. However, in this review we outline potential approaches for tailoring the use of chemotherapy agents to the specific molecular characteristics of individual tumours by performing patient-specific simulations of drug-induced apoptotic signalling. By incorporating multiple layers of information about tumour-specific aberrations, including expression as well as mutation data, these models have the potential to rationalize the selection of chemotherapeutics contained within multi-agent treatment regimens and ensure the optimum response is achieved for each individual patient. [ABSTRACT FROM AUTHOR]

• The leishmanicidal activity of a triazole-phthalimide derivative (PT4) was evaluated. • PT4 decrease the growth and survival of promastigote and amastigotes. • PT4 showed inhibitory potential over the CYP51 enzyme of Leishmania spp. • PT4 induced an increase in ROS and depolarization of the mitochondrial membrane. • Our results pointed PT4 as a promissory agent against Cutaneous Leishmaniasis. Organic compounds obtained by click chemistry reactions have demonstrated a broad spectrum of biological activities being widely applied for the development of molecules against pathogens of medical and veterinary importance. Cutaneous leishmaniasis (CL), caused by intracellular protozoa parasite of genus Leishmania , comprises a complex of clinical manifestations that affect the skin and mucous membranes. The available drugs for the treatment are toxic and costly, with long periods of treatment, and the emergence of resistant strains has been reported. In this study we investigated the in vitro effects of a phthalimide-1,2,3-triazole derivative, the 4-Phenyl-1-[2-(phthalimido-2-yl)ethyl]-1H-1,2,3-triazole (PT4) obtained by click chemistry , on mammalian cells and on L. amazonensis and L. braziliensis , the causative agents of CL in Brazil. In silico ADMET evaluation of PT4 showed that this molecule has good pharmacokinetic properties with no violation of Lipinski's rules. The in vitro assays showed that PT4 was more selective for both Leishmania species than to mammalian cells. This compound also presented low cytotoxicity to mammalian cells with CC 50 > 500 μM. Treatment of promastigote forms with different concentrations of PT4 resulted in ultrastructural alterations, such as plasma membrane wrinkling, shortening of cell body, increased cell volume and cell rupture. The molecular dynamic simulations showed that PT4 interacts with Lanosterol 14 α-demethylase from Leishmania, an essential enzyme of lipid synthesis pathway in this parasite. Our results demonstrated PT4 was effective against both species of Leishmania. PT4 caused a decrease of mitochondrial membrane potential and increased production of reactive oxygen species, which may lead to parasite death. Taken together, our results pointed PT4 as promissing therapeutic agent against CL. [ABSTRACT FROM AUTHOR]