Molecular docking studies of quercetin and its analogues against human inducible nitric oxide synthase

Pharmacophore modeling and 3D-Quantitative Structure Activity Relationship (3D-QSAR) studies have been performed on a dataset of thirty-two quinazoline and aminopyridine derivatives to get an insight into the important structural features required for binding to inducible nitric oxide synthase (iNOS). A four-point CPH (Common Pharmacophore Hypothesis), AHPR.29, with a hydrogen bond acceptor, hydrophobic group, positively charged ionizable group and an aromatic ring, has been obtained as the best pharmacophore model. Satisfactory statistical parameters of correlation ([Formula: see text]) and cross-validated ([Formula: see text]) correlation coefficients, 0.9288 and 0.6353, respectively, show high robustness and good predictive ability of our selected model. The contour maps have been developed from this model and the analysis has provided an interpretable explanation of the effect that various features and substituents have on the potency and selectivity of inhibitors towards iNOS. Docking studies have also been performed in order to analyze the interactions between the enzyme and the inhibitors. Our proposed model can thus be further used for screening a large database of compounds and design new iNOS inhibitors.

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The Discovery of Potentially Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: A Combination of Pharmacophore Modelling, CoMFA, Virtual Screening and Molecular Docking Studies

International Journal of Molecular Sciences ◽

10.3390/ijms15058553 ◽

2014 ◽

Vol 15 (5) ◽

pp. 8553-8569 ◽

Cited By ~ 8

Author(s):

Guanhong Xu ◽

Yue Chen ◽

Kun Shen ◽

Xiuzhen Wang ◽

Fei Li ◽

...

Keyword(s):

Nitric Oxide ◽

Molecular Docking ◽

Nitric Oxide Synthase ◽

Virtual Screening ◽

Neuronal Nitric Oxide Synthase ◽

Docking Studies ◽

Molecular Docking Studies ◽

Pharmacophore Modelling ◽

Oxide Synthase

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MOLECULAR DYNAMIC SIMULATION OF ASIATIC ACID DERIVATIVES COMPLEX WITH INDUCIBLE NITRIC OXIDE SYNTHASE ENZYME AS AN ANTI-INFLAMMATORY

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021.v13s3.06 ◽

2021 ◽

pp. 32-38

Author(s):

IDA MUSFIROH ◽

HANIFAHZIN KHATAMI ◽

SANDRA MEGANTARA ◽

MUCHTARIDI MUCHTARIDI

Keyword(s):

Nitric Oxide ◽

Molecular Dynamics ◽

Molecular Docking ◽

Nitric Oxide Synthase ◽

Binding Affinity ◽

Inducible Nitric Oxide Synthase ◽

Asiatic Acid ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Objective: The aim of this study was to determine the stability interaction of asiatic acid derivatives (AA) complex with inducible nitric oxide synthase (iNOS) enzyme as an anti-inflammatory using Molecular Dynamic (MD) simulation. Methods: The methods were consisting of validation of molecular docking, molecular docking to calculate binding affinity within the complex between the compounds and iNOS enzyme by using MMGBSA (Molecular Mechanics/Generalized Born Surface Area), and MD system preparation, MD production as well as MD analysis using AMBER18. Results: The result of validation and molecular docking were AA5 has the most negative Gibbs energy that is -9.17 kcal/mol, which has better binding affinity than other derivatives than other derivatives. The molecular dynamics simulation of the modified structure of asiatic acid showed that binding energy value and RMSD of AA5, AA6 and AA9 have a lower value compared to arginine as a substrate of iNOS enzyme. Molecular Dynamics that have been occurred to the best three compounds chosen shown good result in terms of stability after 100 ns length simulation. And the lowest binding affinity has been achieved by a compound called AA5. Out of all ligands that have been simulated shown that their binding affinity was lower than AA5 that reached-44.6753 kcal/mol. Conclusion: This studies conclude that AA5 considerably more potential as a selective inhibitor of iNOS enzyme as an anti-inflammatory.

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Molecular Docking Prediction and in Vitro Studies Elucidate Anti-inflammatory Effect of Garcinia Extract Against Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Targets

10.21203/rs.3.rs-794705/v1 ◽

2021 ◽

Author(s):

Anuradha Kalita ◽

MANAS DAS ◽

Bhabajyoti Das ◽

Momita Rani Baro

Keyword(s):

Nitric Oxide ◽

Molecular Docking ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Cyclooxygenase 2 ◽

Herbal Extract ◽

Cox 2 ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Abstract Garcinia is a tropical plant that has been traditionally used in medicinal folklore for its potential antioxidant, antibacterial, anti-hyperlipidemic, anti-diabetic, hepatoprotective, etc. In this study, Garcinia herbal extract (GHE) and one of its important phytocompound (garcinol) were evaluated for their inhibitory action against important inflammatory markers inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. iNOS and COX-2 plays an major role in the process of inflammation and inhibition of these molecules will help to alleviate the inflammatory process. The cells were pre-treated with two doses of Garcinia (230µg/ml and 115µg/ml); garcinol (12µM and 6µM) followed by stimulation with 1µg/ml of LPS for 24h. The results of the study demonstrated that GHE and garcinol plays an important role in suppressing LPS- induced relative mRNA expression of iNOS, COX-2 and subsequent reduction in the levels of nitric oxide and prostaglandin E 2 . Molecular docking analysis of garcinol and hydroxycitric acid, the major active components of GHE with iNOS and COX-2 proteins showed potent interaction with low binding energies. This study suggests that GHE (containing high percentage of HCA) and garcinol may possess anti-inflammatory activity thus providing a possibility for drug designing as iNOS and COX-2 inhibitors.

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Synthesis, Biological Evaluation, and Docking Studies of N-Substituted Acetamidines as Selective Inhibitors of Inducible Nitric Oxide Synthase

Journal of Medicinal Chemistry ◽

10.1021/jm800846u ◽

2009 ◽

Vol 52 (5) ◽

pp. 1481-1485 ◽

Cited By ~ 23

Author(s):

Cristina Maccallini ◽

Antonia Patruno ◽

Neva Bešker ◽

Jamila Isabella Alì ◽

Alessandra Ammazzalorso ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Docking Studies ◽

Biological Evaluation ◽

Selective Inhibitors ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages

Molecules ◽

10.3390/molecules25010013 ◽

2019 ◽

Vol 25 (1) ◽

pp. 13 ◽

Cited By ~ 1

Author(s):

Samreen Soomro ◽

M. Ahmed Mesaik ◽

Farzana Shaheen ◽

Noureen Khan ◽

Sobia Ahsan Halim ◽

...

Keyword(s):

Nitric Oxide ◽

Hydrogen Peroxide ◽

Transcription Factor ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Docking Studies ◽

In Silico Docking ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide

(1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Myrthus communis Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Furthermore, the effects of the compound were analyzed via phosphorylation and translocation of the transcription factor NF kappa B, which is a key regulator of iNOS activation. The effect of MCA-1 on the inducible nitric oxide synthase (iNOS) enzyme was also examined using in silico docking studies. The anticancer potential for MCA-1 was evaluated with an MTT cytotoxic assay. (3) Results: In stimulated macrophages, MCA-1 inhibited superoxide production by 48%, hydrogen peroxide by 53%, and nitric oxide (NO) with an IC50 of <1 µg/mL. MCA-1 also showed a very strong binding pattern within the active site of the inducible nitric oxide synthase enzyme. Furthermore, 25 µg/mL of MCA-1 inhibited inducible nitric oxide synthase expression and abolished transcription factor (NFκB) phosphorylation and translocation to the nucleus. Cytotoxicity analyses of MCA-1 on 3T3 mouse fibroblasts, CC1 liver cell line, J774.2, macrophages and MDBK bovine kidney epithelial cell, yielded IC50 values of 6.53 ± 1.2, 4.6 ± 0.7, 5 ± 0.8, and 4.6 ± 0.7, µg/mL, respectively. (4) Conclusion: Our results suggest that MCA-1, a major phloroglucinol-type compound, shows strong anti-inflammatory activity and has a potential to be a leading therapeutic agent in the future.

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