Interactions between carbon nanotubes and external structures of SARS-CoV-2 using molecular docking and molecular dynamics.

Molecular modeling techniques are used to describe the process of interaction between nanotubes and the main structures of the Covid-19 virus: the envelope protein, the main protease, and the Spike glycoprotein. Molecular docking studies show that the ligands have interaction characteristics capable of adsorbing the structures. Molecular dynamics simulations provide information on the mean squared deviation of atomic positions ​​between 0.5 and 3.0 Å. The Gibbs free energy model and solvent accessible surface area approaches are used. Through the results obtained through molecular dynamics simulations, it is noted that the zig-zag nanotube prefers to interact with E-pro, M-pro, and S-gly, respectively. Molecular couplings and free energy showed that the S-gly active site residues strongly interact with zigzag, chiral, and armchair nanotubes, in this order. The interactions demonstrated in this manuscript may predict some promising candidates for virus antagonists, which may be confirmed through experimental approaches.

New derivative of trans-dehydrocrotonin isolated from Croton cajucara shows reduced cytotoxic and genotoxic effects in hepatocellular carcinoma (HepG2) cell line.

The Croton cajucara (Euphorbiales, Euphorbiaceae) plant occurs widely in the Amazon region, where its leaves and stem bark are consumed by the population to treat several diseases. The secondary metabolite trans-dehydrocrotonin (DCTN) is mainly accountable for the biological activities of this plant. However, prolonged consumption is associated with hepatotoxic effects due to the furan ring present in the molecule. This group is responsible for toxicity reactions in other drugs. In this work, we inserted a COOH group into the molecule to prevent the formation of toxic intermediates. We assessed the cytotoxicity and genotoxicity of both molecules on HepG2 cells. Results showed that the new derivative (CCTN) is less cytotoxic and did not reduce cell viability at any concentration tested. Genotoxicity was also reduced as assessed by the comet and micronucleus assay. Therefore, the new derivative appears to be promising and additional tests should be performed to evaluate its therapeutic activities.

New nanocarried phenobarbital formulation: Maintains better control of pentylenetetrazole-Induced seizures.

This study aims to evaluate the efficacy of slow release phenobarbital in the control of convulsions triggered by pentylenetetrazole (PTZ), verifying the time of permanence in the anticonvulsant effect through behavior and electroencephalographic records. A total of 162 male Wistar rats weighing between 100 and 120 g were divided into two groups, one for behavior analysis (n = 90) and biochemistry, and another for the acquisition of electrocorticographic record (n = 72). Hepatic enzymes were measured by obtaining a blood sample from the animals studied by means of a biochemical analysis. The procedures for electrode implant and electrocorticographic recordings were performed. The intercalation of phenobarbital in layered double hydroxide (LDH) nanocarrier allowed us to evaluate a new slow release pharmaceutical formulation based on methodologies that have proven longer residence time and lower side effects. This study demonstrates that phenobarbital can be a new perspective pharmaceutical formulation.

Theoretical and practical study of the cefoxitin-Escherichia coli PBP5 complex interaction by molecular dynamics to obtain computational prototype of antimicrobial susceptibility to Gram negative bacteria.

The penicillin-binding proteins (PBPs) are important biological target for new antibacterial drugs development. This study focused on molecular interaction between cefoxitin and the Escherichia coli PBP5 by molecular dynamics (MD) using hybrid quantum mechanics/molecular mechanics (QM/MM) simulations approach, searching to develop a computational simulations prototype method on antimicrobial susceptibility of gram-negative bacteria against antibiotics. Escherichia coliATCC 8739 strain susceptibility for the drugs used in the antimicrobial susceptibility testing and selection of bioactive molecules against resistant strain. The protonation revealed a deprotonate state for His146, His151, His216, and His320 residues. The complex was stabilized after 0.6 ns of MD simulation. The global interaction means for inhibition zone diameters of E. coliATCC8739 strain and cefoxitin were 24.33 mm no showing significant difference between computational and experimental methods. Our computational simulation method can reliably be performed as a molecular modeling prototype for gram-negative antimicrobial susceptibility testing bacteria.

An In Silico Study of the Antioxidant Ability for Two Caffeine Analogs Using Molecular Docking and Quantum Chemical Methods.

The antioxidant activity of molecules constitutes an important factor for the regulation of redox homeostasis and reduction of the oxidative stress. Cells affected by oxidative stress can undergo genetic alteration, causing structural changes and promoting the onset of chronic diseases, such as cancer. We have performed an in silico study to evaluate the antioxidant potential of two molecules of the zinc database: ZINC08706191 (Z91) and ZINC08992920 (Z20). Molecular docking, quantum chemical calculations (HF/6-31G**) and Pearson's correlation have been performed. Molecular docking results of Z91 and Z20 showed both the lower binding affinity (BA) and inhibition constant (Ki) values for the receptor-ligand interactions in the three tested enzymes (cytochrome P450-CP450, myeloperoxidase-MP and NADPH oxidase-NO) than the control molecules (5-fluorouracil-FLU, melatonin-MEL and dextromethorphan-DEX, for each receptor respectively). Molecular descriptors were correlated with Ki and strong correlations were observed for the CP450, MP and NO receptors. These and other results attest the significant antioxidant ability of Z91 and Z20, that may be indicated for further analyses in relation to the control of oxidative stress and as possible antioxidant agents to be used in the pharmaceutical industry.

Trans-4-methoxy-ß-nitrostyrene relaxes rat thoracic aorta through a sGC-dependent pathway.

1-Nitro-2-phenylethene (NPe) induces a more potent vasorelaxant effect in rat aorta than its structural analog 1-nitro-2-phenylethane, but mediated through a different mechanism, independent of soluble guanylate cyclase (sGC) stimulation. We hypothesized that introducing an electron donor into the aromatic moiety might stabilize NPe, enhancing its potency and/or interaction with sGC. Therefore, trans-4-methoxy-ß-nitrostyrene (T4MN) was synthesized, and mechanisms underlying its vasorelaxant effects were studied in rat aortic ring preparations. In endothelium-intact preparations, T4MN fully relaxed contractions induced by phenylephrine (PHE) with a potency similar to that of its parent drug, NPe. This vasorelaxant effect that was unchanged by endothelium removal, pretreatment with L-NAME, indomethacin, or MDL-12,330A, but was significantly reduced by tetraethylammonium, 4-aminopyridine, methyl blue, or ODQ. Under Ca2+-free conditions, T4MN did not alter contractions evoked by caffeine, but significantly reduced, in an ODQ-preventable manner, those induced by either PHE or extracellular Ca2+ restoration following depletion of intracellular Ca2+ stores in thapsigargin-treated aortic preparations. Under the same conditions, T4MN also reduced contractions induced by protein kinase C activator phorbol-12,13-dibutyrate with a potency similar to that evoked by this nitroderivative against PHE-induced contractions. In conclusion, T4MN induces potent vasorelaxation in rat aorta by stimulating the sGC-cGMP pathway through a NO-independent mechanism. Introduction of a methoxy group into the aromatic moiety apparently stabilizes NPe, thereby enhancing its interaction with sGC.

Diet enriched with the Amazon fruit açaí (Euterpe oleracea) prevents electrophysiological deficits and oxidative stress induced by methyl-mercury in the rat retina.

BACKGROUND: The protective effect of a diet supplemented by the Amazonian fruit Euterpe oleracea (EO) against methylmercury (MeHg) toxicity in rat retina was studied using electroretinography (ERG) and biochemical evaluation of oxidative stress. METHOD: Wistar rats were submitted to conventional diet or EO-enriched diet for 28 days. After that, each group received saline solution or 5 mg/kg/day of MeHg for 7 days. Full-field single flash, flash and flicker ERGs were evaluated in the following groups: control, EO, MeHg, and EO+MeHg. The amplitudes of the a-wave, b-wave, photopic negative response from rod and/or cone were measured by ERGs as well as the amplitudes and phases of the fundamental component of the sine-wave flicker ERG. Lipid peroxidation was determined by thiobarbituric acid reactive species. RESULTS: All ERG components had decreased amplitudes in the MeHg group when compared with controls. EO-enriched food had no effect on the non-intoxicated animals. The intoxicated animals and those that received the supplemented diet presented significant amplitude reductions of the cone b-wave and of the fundamental flicker component when compared with non-intoxicated control. The protective effect of the diet on scotopic conditions was only observed for bright flashes eliciting a mixed rod and cone response. There was a significant increase of lipid peroxidation in the retina from animals exposed to MeHg and EO-supplemented diet was able to prevent MeHg-induced oxidative stress in retinal tissue. CONCLUSION: These findings open up perspectives for the use of diets supplemented with EO as a protective strategy against visual damage induced by MeHg.

Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients.

INTRODUCTION: The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS) in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. METHODS: We evaluated the nitric oxide (NO) concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD) in leprosy patients. RESULTS: We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. CONCLUSIONS: The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients.

Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients

Introduction The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS) in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. Methods We evaluated the nitric oxide (NO) concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD) in leprosy patients. Results We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. Conclusions The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients. .