Neurodegenerative diseases, such as Parkinson's and Alzheimer's, are understood as occurring through genetic, cellular, and multifactor pathophysiological mechanisms. Several natural products such as flavonoids have been reported in the literature for having the capacity to cross the blood-brain barrier and slow the progression of such diseases. The present article reports on in silico enzymatic target studies and natural products as inhibitors for the treatment of Parkinson's and Alzheimer's diseases. In this study we evaluated 39 flavonoids using prediction of molecular properties and in silico docking studies, while comparing against 7 standard reference compounds: 4 for Parkinson's and 3 for Alzheimer's. Osiris analysis revealed that most of the flavonoids presented no toxicity and good absorption parameters. The Parkinson's docking results using selected flavonoids as compared to the standards with four proteins revealed similar binding energies, indicating that the compounds 8-prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, capensinidin, and rosinidin are potential leads with the necessary pharmacological and structural properties to be drug candidates. The Alzheimer's docking results suggested that seven of the 39 flavonoids studied, being those with the best molecular docking results, presenting no toxicity risks, and having good absorption rates (8-prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, aspalathin, butin, and norartocarpetin) for the targets analyzed, are the flavonoids which possess the most adequate pharmacological profiles.

Background: Tuberculosis is a disease with high incidence and high mortality rate, especially in Brazil. Although there are several medications available for treatment, in cases of resistance, there is a need to use more than one medication. Objective: Therefore, cases of toxicity increase and reports of resistance have been worrying the population. In addition, some medications have a short period of effectiveness. To achieve the goal, ligand-based and structure-based approaches were used. Method: Thus, in an attempt to discover potent inhibitors against Mycobacterium tuberculosis enzymes, we sought to identify natural products with high therapeutic potential for the treatment of Tuberculosis through QSAR, Molecular Modeling and ADMET studies. Results: The results showed that the models generated from two sets of molecules with known activity against M. tuberculosis enzymes InhA and PS were able to select 11 and 8 compounds respectively, between Lignans and Neolignans with 50 to 60% activity probability. In addition, molecular docking contributed to confirm the mechanism of action of compounds and increase the accuracy of methodologies. All molecules showed higher binding energy values for the drug Isoniazid. We conclude that compounds 33, 34, 110, 114, 133 are promising for InhA target and compounds 07, 08, 19, 21, 42, 48, 75 and 141 for target PS. In addition, most molecules did not show any toxicity according to the evaluated parameters. Conclusions: Therefore, Lignans and Neolignans may be an alternative for the treatment of Tuberculosis.

Background: Metabolic disorders are a major cause of illness and death worldwide. Metabolism is the process by which the body makes energy from proteins, carbohydrates, and fats; chemically breaking these down in the digestive system towards sugars and acids which constitute the human body's fuel for immediate use, or to store in body tissues, such as the liver, muscles, and body fat. Objective: The efficiency of treatments for multifactor diseases has not been proved. It is accepted that to manage multifactor diseases, simultaneous modulation of multiple targets is required leading to the development of new strategies for discovery and development of drugs against metabolic disorders. Methods: In silico studies are increasingly being applied by researchers due to reductions in time and costs for new prototype synthesis; obtaining substances that present better therapeutic profiles. Discussion: In the present work, in addition to discussing multi-target drug discovery and the contributions of in silico studies to rational bioactive planning against metabolic disorders such as diabetes and obesity, we review various in silico study contributions to the fight against human metabolic pathologies. Conclusion: In this review, we have presented various studies involved in the treatment of metabolic disorders; attempting to obtain hybrid molecules with pharmacological activity against various targets and expanding biological activity by using different mechanisms of action to treat a single pathology.

AIDS is a chronic infection that compromises the immune system of the individual infected with HIV. HIV is a retrovirus, that is, it has RNA as a genetic material, and needs the action of reverse transcriptase (RT) to multiply. A nucleoside is formed by the bond between a carbohydrate and a nitrogenous base that is inserted into the genetic material preventing multiplication. This work consists of a computational analysis through Molecular Docking in order to predict the potential inhibitory activity of RT from a series of 24 nucleoside analogs derived from fructopyranose compared to the bioactive molecules already inserted in the anti-HIV treatment. For this study 36 molecules were designed in ChemDraw Ultra 12.0 to obtain its 2D structural formula. Then the molecule was optimized MM + and AM1 using HyperChemTM (Release 8.0.6 for Windows). Finally, the enzyme RT in PBD (PDB ID 1REV) was selected and in Molegro Virtual Docking 6.0 anchorage was performed. It is possible to conclude that some molecules presented favorable energies for the formation of the ligand-enzyme complexes, as well as the presence of interactions with amino acid residues common to known inhibitors.

AIDS is an infectious disease characterized by compromised defense cells, is caused by Human Immunodeficiency Virus -HIV, which affects about 36.7 million people. In its viral multiplication process, HIV requires protease, integrase and reverse transcriptase which are important enzymes in the process. Many therapeutic alternatives in the anti-HIV treatment are in the inhibition of these enzymes, many researches are being directed towards the search of new inhibitors that present better pharmacological profiles. The use of natural products in anti-HIV research has been growing substantially, research groups are betting on these substances in an attempt to offer potent drugs with reduced side effects. The objective of this study was to carry out chemoinformatic studies using cytotoxicity risk prediction tools; prediction of absorption and molecular docking of natural products found in the database of chemical structures (ChEMBL) and literature. The interactions with the targets, the% ABS and cytotoxicological analysis were evaluated. 243 natural products and 18 anti-HIV drugs were analyzed. All molecules had their 3D structures optimized by the methods of mechanical molecules (MM+) and Semi-empirical methods (AM1) (RMS 0.1 kcal /Å.mol in 600 cycles) through HyperChemTM 8.0 software. Structures were imported into the software OSIRIS DataWarrior 4.3.7 for prediction of cytotoxicity risks and absorption rate was calculated based on TPSA. Finally, molecular docking was performed using the software Molegro Virtual Docker 6.0 to calculate the energies of interaction with the protease receptors (PDB ID: 1OHR; reverse transcriptase PDB ID: 1REV and integrase (PDB ID: 3WNH). Of the 243 molecules of natural products with anti-HIV activity, 7 were promising because they did not present cytotoxicity risks (mutagenicity, carcinogenicity, skin irritability and reproductive system effect), better MolDockScore energies for all targets studied simultaneously by varying the interaction energies binder-receptor of -209.47kJ.mol -1 at -60.20kJ.mol -1 and absorption rate (% ABS) between 34.26% and 90.24%.