| ORIGINAL ARTICLE |
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| Year : 2019 | Volume
: 15
| Issue : 64 | Page : 280-287 |
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Potential Cyclooxygenase (COX-2) enzyme inhibitors from Myrica nagi-from in-silico to in-vitro investigation
HP Prashanth Kumar1, Prachurjya Panda2, Prashantha Karunakar3, Kotikalapudi Shiksha2, Laxmi Singh2, Nijalingappa Ramesh1, Talambedu Usha4, Sushil Kumar Middha2
1 Department of Biotechnology, School of Applied Sciences, Reva University, Bengaluru, Karnataka, India
2 Department of Biochemistry and Biotechnology, Maharani Lakshmi Ammanni College for Women, Bengaluru, Karnataka, India
3 Department of Biotechnology, PES University, Bengaluru, Karnataka, India
4 Department of Biochemistry, Bangalore University, Bengaluru, Karnataka, India
Correspondence Address:
Sushil Kumar Middha
Department of Biochemistry and Biotechnology, Maharani Lakshmi Ammanni College for Women, Bengaluru, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/pm.pm_56_19
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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.
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