IN SILICO ADME ANALYSIS AND MOLECULAR DOCKING OF PHYTOCHEMICALS FROM MORINDA CITRIFOLIA WITH ONCOGENIC SHP2 PROTEIN

Chandru P, Nandhana R, Ganapathy CA, Selvamuthukumar R, Saminathan C

SHP2 (Src homology 2 domain-containing phosphatase 2) is a protein tyrosine phosphatase that plays a major role in the activation of various cell signaling pathways such as RAS/Raf/MAPK, PI3K/AKT, mTOR. Over activating mutation or excessive overexpression of SHP2 is linked with metastasis and tumorigenesis. Identification of active site inhibitors for SHP2 protein is quite challenging as the catalytic site is enriched with a positively charged environment. To overcome this, allosteric inhibition of the SHP2 protein in auto-inhibited conformation is considered. Here, we used the phytochemicals which are found to be present in the leaf extract of Morinda citrifolia to target the SHP2 protein. The ADME properties of those phytochemicals were studied using the SwissADME tool. Molecular docking of potent phytochemicals was performed with SHP2 protein (PDB - 5EHR) using AutoDock tools. 18 phytochemicals which are found to be present in the leaf extract of Morinda citrifolia were selected for SwissADME analysis and result showed that four phytochemicals (Minaprine, Mycophenolic acid, Pilocarpine and Scopolamine) were found to possess drug-likeness and good oral bioavailability. Molecular docking of Minaprine, Mycophenolic acid, Pilocarpine and Scopolamine with SHP2 protein shows a good binding affinity of -9.6, -9.32, -6.81and -9.05 kcal/mol at the allosteric site, respectively. This shows that these phytochemicals can be used for the development of potent allosteric inhibitors of SHP2 in the treatment of cancer. In summary, the ADME properties and docking studies with SHP2 protein shown that Minaprine, Mycophenolic acid, Pilocarpine and Scopolamine which is found in the leaf extract of Morinda citrifolia shows good oral bioavailability and inhibitory action. Therefore, these phytochemicals can be used for the treatment of cancer targeting SHP2 protein.

Keywords –Morinda citrifolia, SHP2, Molecular docking, ADME