Food-Related Compounds That Modulate Expression of Inducible Nitric Oxide Synthase May Act as Its Inhibitors

Abstract

Natural compounds commonly found in foods may contribute to protect cells against the deleterious effects of inflammation. These anti-inflammatory properties have been linked to the modulation of transcription factors that control expression of inflammation-related genes, including the inducible nitric oxide synthase (iNOS), rather than a direct inhibitory action on these proteins. In this study, forty two natural dietary compounds, known for their ability to exert an inhibitory effect on the expression of iNOS, have been studied in silico as docking ligands on two available 3D structures for this protein (PDB ID: 3E7G and PDB ID: 1NSI). Natural compounds such as silibinin and cyanidin-3-rutinoside and other flavonoids showed the highest theoretical affinities for iNOS. Docking affinity values calculated for several known iNOS inhibitors significatively correlated with their reported half maximal inhibitory concentrations (R = 0.842, P < 0.0001), suggesting the computational reliability of the predictions made by our docking simulations. Moreover, docking affinity values for potent iNOS inhibitors are of similar magnitude to those obtained for some studied natural products. Results presented here indicate that, in addition to gene expression modulation of proteins involved in inflammation, some chemicals present in food may be acting by direct binding and possible inhibiting actions on iNOS.

Computational fishing of new DNA methyltransferase inhibitors from natural products

“…4. The correlation analysis indicated the inhibition of DNMT1 activity follows a highly dependence with calculated binding scores for these compounds (r= 0.83, p value <0.0001; for binding affinity vs logIC50, r= 0.65, p value <0.0001; for Total score vs logIC50), with correlation coefficients comparable to those reported in other studies for these validations[56,59,60,73] as shown inFig. 4a and Fig.…”

“…Based on these results, two representative DNMTs crystallographic structures were selected for protein-ligand docking protocols: DNMT1 (3SWR) and DNMT3A (2QRV). for best poses was taken as the value of the binding affinity for a particular complex [54,59].…”

Natural Products as Chemopreventive Agents by Potential Inhibition of the Kinase Domain in ErbB Receptors

“…Three docking runs were performed for each ligand, and the pose with the highest Affinity absolute value (kcal/mol) was saved. Finally, the mean Affinity score for best poses was taken as the value of the binding Affinity for a particular complex [ 50 , 51 ].…”

Modulation of the formation of active forms of nitrogen by ingredients of plant products in the inhibition of carcinogenesis

“…БАКРП способны также изменять биотрансформацию канцерогенов, влиять на репарацию ДНК, экспрессию протоонкогенов, пролиферацию и дифференцировку клеток, апоптоз, эндокринный статус организма, систему противоопухолевого иммунитета и др. [6,66,67]. Растительные полифенолы препятствуют прогрессированию канцерогенеза, в том числе за счет избирательного взаимодействия с белками, образуя полифенольно-белковые комплексы, которые могут влиять на активность онкогенных белков-мишеней.…”

“…Растительные полифенолы препятствуют прогрессированию канцерогенеза, в том числе за счет избирательного взаимодействия с белками, образуя полифенольно-белковые комплексы, которые могут влиять на активность онкогенных белков-мишеней. Следует отметить, что в некоторых случаях, особенно при высоких дозах, БАКРП могут инициировать воспаление, повреждение ДНК и оказывать другие побочные эффекты [66,68].…”