Potential Cyclooxygenase (COX-2) enzyme inhibitors from Myrica nagi-from in-silico to in-vitro investigation

Introduction: Myrica nagi Thunb. (family Myricaceae) are actinorhizal plants showing symbiotic interaction with Frankia. Inhibition of cyclooxygenase-2 (COX-2) enzyme is known to be significant in preventing inflammation and in therapeutics. Objectives: Our principal focus was to identify COX-2 enzy...

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Published in:	Pharmacognosy Magazine Vol. 15; no. 64; pp. 280 - 287
Main Authors:	Prashanth Kumar, H, Panda, Prachurjya, Karunakar, Prashantha, Shiksha, Kotikalapudi, Singh, Laxmi, Ramesh, Nijalingappa, Usha, Talambedu, Middha, Sushil
Format:	Journal Article
Language:	English
Published:	London Wolters Kluwer India Pvt. Ltd 01-07-2019 Medknow Publications and Media Pvt. Ltd Sage Publications Ltd
Subjects:	Anti-inflammatory agents Binding sites Biological activity Cancer Chemical properties COX-2 inhibitors Cytotoxicity DNA polymerase Energy (Physics) Enzyme inhibitors Enzymes Flavonoids Genetic algorithms Health aspects Hydrogen bonds Identification and classification Inflammation Kinases Laboratories Leukemia Ligands Metabolism Metabolites Myricaceae NMR Nuclear magnetic resonance Pharmacognosy Pharmacological research Phytochemicals Plants (Organisms) Proteins Studies Therapeutics Ulcers India docking intermolecular energy myricetin cyclooxygenase 2 inhibitory concentration flavonoids Anti-inflammatory
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Summary:	Introduction: Myrica nagi Thunb. (family Myricaceae) are actinorhizal plants showing symbiotic interaction with Frankia. Inhibition of cyclooxygenase-2 (COX-2) enzyme is known to be significant in preventing inflammation and in therapeutics. Objectives: Our principal focus was to identify COX-2 enzyme inhibitors, safer and natural anti-inflammatory compounds from M. nagi. Protein-ligand interaction has a significant role in structure-based drug design. Materials and Methods: Sixty-eight phytochemicals were therefore screened and evaluated for their binding energies with COX-2. These phytoconstituents were screened and analyzed for drug Likeliness along with Lipinski's rule of five. The X-ray crystallographic structure of the target COX-2 (protein data bank [PDB] ID: 4PH9), obtained from PDB, was docked with PubChem structures of phytochemicals using AutoDock 4.2 that uses Lamarckian genetic algorithm. Further, myricetin was subjected to in vitro anti-inflammatory assay using RAW-264.7 cell lines and inhibitory concentration (IC50) value was also determined. Results: The myricetin, myricitrin, and corchoionoside-C inhibited COX-2 with − 6.52, −4.94, and − 4.94 Kcal/mol binding energies, respectively, comparable to ibuprofen. Eventually, bioactivity score and absorption distribution metabolism excretion-toxicity properties showed considerable biological activities as G protein-coupled receptor, nuclear receptor, protease inhibitor, and enzyme inhibitors for myricetin, myricitrin, and corchoionoside-C phytochemicals. Molecular docking revealed hydrophobic interactions followed by four, nine, and four numbers of hydrogen bonds between myricetin, myricitrin, and corchoionoside-C, respectively, within the binding site of COX-2. Flavonol myricetin showed 112 μg/mL as IC50 value when it was subjected to in vitro cytotoxicity assay. These results clearly demonstrated that myricetin, myricitrin, and corchoionoside-C could act as highly potential COX-2 inhibitors. Therefore, in silico and in vitro studies revealed that of three best phytochemicals, myricetin could be promising candidate.
ISSN:	0973-1296 0976-4062
DOI:	10.4103/pm.pm_56_19