Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: −17.65 kcal mol⁻¹ (D6), −18.07 kcal mol⁻¹ (D2), −18.13 (D5) kcal mol⁻¹, and −10.31 kcal mol⁻¹ (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (−12.84 kcal mol⁻¹) and L-tyrosine (−9.04 kcal mol⁻¹) in melanogenesis.

Structural and energetic features explain why some drugs can be repositioned to inhibit M ^pro from SARS-CoV-2.

• Ethanol extract of Eleutherine plicata showed low in vitro and in vivo cytotoxic potential. • The dichloromethane fraction was cytotoxic to HepG2 and caused DNA. However, no toxicity was observed in vivo. • Isoeleutherin caused DNA damage by the comet method and activated caspase-8 in the in silico study.

Background:: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3- phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease.Objective:: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana).Methods: A search for novel antileishmanial molecules was carried out based on similarities from the pharmacophoric point of view related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations.Results:: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity.Conclusion:: he use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.

This work reports the influence of a reduced graphene oxide (rGO) support on the catalytic performance of Cu@PtRu/rGO electrocatalysts toward methanol oxidation in an acidic medium. These electrocatalysts are synthesized via a two-step reduction method; the first step utilizes ethylene glycol for the reduction of Cu²⁺ ions, forming Cu/rGO. In the second step, spontaneous redox reactions take place, in a process known as galvanic displacement, where the Pt²⁺ and Ru³⁺ species are reduced to form PtRu layers, and the copper is partially oxidized to the solution. Then, the Cu@PtRu/rGO core–shell is produced, comprising Cu in the inner structure (core) and PtRu on the outer part (shell). To compare the catalytic performance of the prepared nanocatalysts (NCs), Pt/C, PtRu/C, and Cu@PtRu/C are also synthesized on Vulcan XC-72R carbon. All catalysts are characterized via X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Cyclic voltammetry (CV) and chronoamperometry (CA) are employed to measure the electrochemical performance. The core–shell/rGO combination is superior in catalytic activity to the traditional Pt/C, PtRu/C, and Cu@PtRu/C catalysts for the methanol oxidation reaction. These results suggest that Cu@PtRu/rGO exhibits a high bulk activity for methanol electrooxidation, a high stability, and a high tolerance to CO poisoning, meaning it is possible to reduce the platinum loading in proton-exchange membrane fuel cells (PEMFCs).