In silico modelling of the interaction of <i>Murrayanina </i>(3-formil-1-metoxicarbazol) with human phospholipase A2
Creators: name: Bedoya, Jose Miguel Pedroza
name: Ugarriza, Mauricio Ernesto Orozco
name: Yenifer Olivo Martínez
Publisher: name: F1000Research
Year: 2017

description: Approximately 80% of the world's population routinely uses traditional medicine to meet their primary health care needs, using plant extracts or their active ingredients. The species Murraya paniculata is native to India, belongs to the family Rutaceae and has uses as a medicinal and ornamental plant, traditionally recognized for its astringent, stimulating, analgesic, anti-inflammatory properties, among others in some Colombian communities for pain relief and inflammation associated with osteomioarticular diseases.<br><br>Plant biodiversity represents an inexhaustible source of new molecules with biological activity. Among this diversity we have species belonging to the genus Murraya, which originates in India, belongs to the Rutaceae family and has uses as a medicinal and ornamental plant, traditionally recognized For its astringent, stimulating, analgesic, anti-inflammatory properties, among others. In some Colombian communities it is used for the relief of pain and inflammation associated with osteomioarticular diseases. A group of enzymes that has focused on the mechanisms of inhibition by active metabolites are the Phospholipases A2 (FLA2), through molecular docking-docking molecular studies, which have demonstrated the interaction between protein-ligand and natural products Catalytic site of the FLA2. It has been reported that the extracts obtained from Murraya paniculata (L.) Jack (Rutaceae), present an antagonistic and inhibitory effect on FLA2.<br><br>To evaluate by silico studies the molecular interaction between Murrayanina (3-formyl-1 methoxycarbazole) and the enzyme Phospholipase A2.<br><br>There are few studies in the Colombian Caribbean region that deepen the chemical composition of the species of the genus Murraya, nor do they relate to ethnomedical information and biological activities. Preliminary studies have demonstrated its antagonistic and inhibitory effect of mediators of inflammation. To evaluate the analgesic and anti-inflammatory effect of the essential oil extracted from the <i>Murraya sp</i>. in female Wistar rats. The 3D structure of the enzyme FLA 2 (PDBID-1POE) was obtained from the Protein Data Bank server (http://www.rcsb.org/) and the DeepView program is also used (http: //spdbv.vital-it .ch /) for analysis and visualization. The Carbazole structure of Murrayanina (3-formyl-1-methoxycarbazole), isolated from <i>Murraya sp</i>. was obtained in SMILES and MDL Mol format from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/). The molecular properties of the Murrayanina were calculated based on molecular descriptors and analyzed according to the rule of five of Lipinski with the server Molinspiration Online Property Calculation Toolkit, (http://www.molinspiration.com). The study of the interaction between Murrayanina and the FLA 2 enzyme was performed by molecular docking, using the online server Mcule © (https://mcule.com). <i>In silico</i>prediction of the properties of ADME / Tox (Absorption, Tissue Distribution, Metabolism, Excretion and Toxicity) with the AdmetSAR server tool-Admet structure-activity relationship (http://lmmd.ecust.edu.cn:8000/). According to the preliminary results described above, it has been shown through molecular modeling that Murrayanin possesses a potent anti-inflammatory activity, mediated mainly by the inhibitory activity on the enzyme FLA2s, showing that it selectively blocks the active site of this protein, but represents a risk Category IV oral toxicity potential if the concentration of 1250 mg / kg is exceeded. Further studies of enzyme inhibition <i>in vitro</i> and <i>in vivo</i> are necessary to confirm this hypothesis.