Evaluación in silico del efecto de compuestos fenólicos de Pleurotus ostreatus sobre la enzima 5-lipoxigenasa (5- LOX) / In silico evaluation of the effect of Pleurotus ostreatus phenolic compounds on the enzyme 5-lipoxygenase (5-LOX)

Introducción: Los hongos comestibles, en particular Pleurotus ostreatus, representan una importante fuente de metabolitos bioactivos con propiedades inmunomoduladoras, antioxidantes y antiinflamatorias. Trabajos recientes han demostrado que extractos y compuestos purificados a partir de esta seta, entre ellos, la fracción rica en fenoles, inhiben el factor nuclear kappa B(NF-κB), la cicloxigenasa (COX) y modulan cascadas de señalización relacionadas con el balance redox. De acuerdo con estos antecedentes, dichos compuestos podrían actuar, además, como inhibidores de la enzima 5- lipoxigenasa (5-LOX). Objetivo: Evaluar el efecto in silico de trece compuestos fenólicos presentes en la especie Pleurotus ostreatus sobre la enzima 5-LOX, al utilizar como compuesto de referencia la mangiferina. Métodos: El acoplamiento se llevó a cabo a través del programa AutoDock 4.2 (http://autodock.scripps.edu) y la estructura de 5 LOX se obtuvo con la base de datos de proteínas, PDB (www.wwpdb.org). Se estimaron la energía libre (ΔG), la constante de disociación (Ki) y la eficiencia de ligando (LE). Se obtuvieron los parámetros de similitud a un fármaco y los relacionados con la absorción, distribución, metabolismo, excreción y toxicidad (ADME/T) de los mejores modelos de acoplamiento. Resultados: Los mejores indicadores de ΔG y Ki, correspondieron a los ácidos homogentísico, clorogénico y gentísico, con valores de ΔG (-11,81; -12,28 y -11,67 kcal/moL) y Ki (2,19 10-9; 9,99 10-10, 2,79 10-9 M), respectivamente. La eficiencia de ligando alcanzó valores adecuados para estos tres compuestos fenólicos. El modelo de acoplamiento del ácido homogentísico mostró los mejores resultados en cuanto a la similitud a un fármaco y pruebas ADME/T. Conclusiones: El estudio in silico reveló las potencialidades de la fracción rica en fenoles de P. ostreatus, y en particular, del ácido homogentísico como inhibidor de la enzima 5 -LOX, y justifica el desarrollo de ensayos confirmativos in vitro/ in vivo que corroboren sus efectos antioxidantes y antinflamatorios(AU)

Introduction: Edible mushrooms, Pleurotus ostreatus in particular, are an important source of bioactive metabolites with immunomodulatory, antioxidant and anti-inflammatory properties. Recent studies have shown that extracts and compounds purified from this mushroom, among them the phenol-rich fraction, inhibit nuclear factor kappa B (NF-κB), cyclooxygenase (COX), and modulate signaling cascades related to redox balance. According to these antecedents, such compounds could also act as inhibitors of the enzyme 5-lipoxygenase (5-LOX). Objective: Evaluate the in silico effect of 13 phenolic compounds present in the species Pleurotus ostreatus on the enzyme 5-LOX using mangiferin as reference compound. Methods: Docking was carried out with the software AutoDock 4.2 (http://autodock.scripps.edu) and the 5-LOX structure was obtained with the protein database PDB (www.wwpdb.org). Estimation was performed of free energy (ΔG), dissociation constant (Kd) and ligand efficiency (LE). Drug-likeness parameters were obtained, as well as those related to absorption, distribution, metabolism, excretion and toxicity (ADMET) of the best docking models. Results: The best ΔG and Kd indicators were homogentisic, chlorogenic and gentisic acids, with ΔG and Kd values of -11.81, -12.28, -11.67 kcal/mol, and 2.19 10-9, 9.99 10-10, 2.79 10-9 M, respectively. Ligand efficiency achieved adequate values for these three phenolic compounds. The docking model for homogentisic acid showed the best results in terms of drug likeness and ADMET tests. Conclusions: The in silico study revealed the potential of the phenol-rich fraction of P. ostreatus, homogentisic acid in particular, as an enzyme 5-LOX inhibitor, and justifies the development of confirmatory in vitro / in vivo assays to corroborate its antioxidant and anti-inflammatory effects(AU)

Investigating Drug Properties Of Bioactive Compounds Of Cymbopogon Citratus By Absorption, Distribution, Metabolism, Excretion/Toxicity And Molecular Docking Analysis Against Apolipoprotein N-Acyl Transferase

Delivering a potential drug is a predominant challenge in medicinal chemistry.in this study, bio organic compounds of Cymbopogon citratus was screened by analysing physiochemical properties like solubility, permeability, efficacy, toxicity, and metabolic stability. The optimization of drug potential against virulent protein was calculated by using docking algorithm Autodock 4.2.3. Structure based ligand docking reveals that the compounds having better inhibition potential against virulent enzymes with insoluble and impermeable activities. The organic compounds of Cymbopogon citratus were screened using Lipinski rule of five and ADME/T prediction for drug likeliness. The structure based ligand docking was done between bioactive compounds of plant and virulent protein that cause diseases. The interaction was visualized using Discovery studio and was studies. The molecular docking of bioactive compounds resulted in better inhibition potential with controlled lipophilicity level, without causing toxicity that harms the natural habitat of humans. The compounds, 1,3,4-trimethyl -3cyclohexene-1-carboxaldehyde exhibit binding energy -4.70 Kcal/mol followed by β-myrcene – 4.35 Kcal/mol and Geraniol -4.35 Kcal/mol. Hence, structure based ligand docking and in silico ADME/T studies revealed that the compounds have better inhibition potential against Apolipoprotein by improving the prediction of drug compounds.

In silico molecular docking and ADME/T analysis of plant compounds against IL17A and IL18 targets in gouty arthritis

Accumulation of urate crystals and subsequent inflammation are the major cause of pathogenesis of gout. Twopro inflammatory cytokines IL17A and IL18 are upregulated in the serum of gout patients and plays a major rolein promoting inflammation. Inhibition of these cytokines by plant phytochemicals would reduce the severity ofinflammation in gout. In the present study, in silico analysis of inhibition of IL17A and IL18 by 10 plant phytochemicalswere studied using the AutoDock 4.2 based on the principles of Lamarckian genetic algorithm. The results revealed abinding energy in the range of −6.32 kcal/mol to −3.5 kcal/mol and interacted with the amino acids in active pocketof IL17A and IL18. Among all the compounds, syringaresinol showing the least binding energy of −6.05 kcal/molwith IL17A and −6.32 kcal/mol with IL18. The control drug, allopurinol showed a binding energy of −3.32 and −3.18kcal/mol with IL17A and IL18, respectively. In addition, ADME/T properties of the compounds were also analyzed topredict their drug likeliness. This docking study can be used for developing potent inhibitors of IL17A and IL18 forthe treatment of gout.

Pharmacodynamic effect and virulent effect of Tripterygium wilfordii based on network pharmacology / 中国中药杂志

To investigate the pharmacodynamic effect and virulent effect of the main components of the toxic Chinese medicine Tripterygium wilfordii,such as triptolide,tripchlorolide,tripterine,demethylzeylasteral,wilfotrine and euonine,the admet SAR online assessment system was used to calculate the properties of the main components of T. wilfordii. The potential targets of the components were mined and collected through multiple databases,and the potential targets were enriched by the bioinformatics database DAVID.Cytoscape software was used to establish a " target-pathway" network and perform topology analysis on the network. The main chemical components of T. wilfordii were able to penetrate the blood-brain barrier and had intestinal permeability. A total of 65 targets were predicted,including pathways in cancer,hepatitis B,rheumatoid arthritis,and chagas disease( American trypanosomiasis),Toll-like receptor signaling pathway,apoptosis,colorectal cancer,NF-kappa B signaling pathway,etc. T. wilfordii mainly plays a role in the treatment of immune diseases and cancer by regulating inflammatory signaling pathways and cancer signaling pathways. Its action on apoptosis pathway and drug metabolism enzymes may be the mechanism of its toxicity.

Binding affinity of asiatic acid derivatives design against Inducible Nitric Oxide Synthase and ADMET Prediction.

Asiatic acid (AA) is a pentacyclic triterpenoid compound isolated from pegagan (Centella asiatica) and is reported to show anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS), an isoenzyme responsible for the catalysis of nitric oxide formation. The aim of this study was to obtain information regarding binding affinity of some potential asiatic acid derivatives to iNOS as well as pharmacokinetic properties including oral absorption, distribution, metabolism, and toxicity (ADME/T) using in silico methods. Twelve AA derivatives that were produced by modeling of AA on A- or C-ring or its carboxylic acid group, were included in this study. The affinities of these compounds were studied using molecular docking methods, while pharmacokinetic properties were studied using the PreADMET online program. The results showed that eight AA derivative designs have lower free energy binding (FEB) in comparison to AA (–9.79 kcal/mol), while four of the compound designs showed higher FEB than AA. 2,3-dioxo-11,13 diene-23-carboxy asiatic acid (7) showed the lowest FEB of -11.33 kcal/mol. This compound has the human intestinal absorption (HIA), Caco-2 cell permeability, and plasma protein binding values of 96.62%, 20.90 (nm/Sec.), and 98.46%, respectively, which are comparable to those of AA and other AA derivatives. It is concluded that 2,3-dioxo-11,13 diene-23-carboxy asiatic acid (7) is an AA derivative with potential to be developed as a potential iNOS inhibitor.