MODULATION OF mTOR RECEPTOR IN DIABETIC NEPHROPATHY BY SANTALIN A OF LAL CHANDAN (PTEROCARPUS SANTALINUS): AN IN-SILICO ASSESSMENT BY MOLECULAR DOCKINGAbstract
Background: Diabetic nephropathy (DN) is a primary cause of end-stage renal disease globally. Activation of mTOR and reduced autophagy has been identified as one of the pathogenic pathways. The presently available drugs have been successful in inhibiting the mTOR signaling, but show low oral bioavailability and suboptimal solubility. Rapamycin is a selective inhibitor of mTOR, shown significant protection against DN. However, its continuous use is associated with side effects. Thus, the search for novel drugs is on great demand. In the present study, in-silico approaches have been adopted to identify potential compounds with optimal oral bioavailability and better solubility properties, with no toxic effect. Materials and method: The receptor protein mTOR with PDB ID: 3FAP was retrieved from the RCSB protein data bank. Total 20 compounds were selected from the list of 113, obtained from LC-MS of Lalchandan. Further, in-silico molecular docking calculation was done by using YASARA software. Drug-likeness and molecular property of best-docked compounds were checked by using Lipinski rule of five and Admet SAR server. Result: Five compounds showed interaction with mTOR protein. Out of these Santalin A showed the best interaction with binding energy 11.453[kcal/mol] and dissociation constant 4025.6841[pM]. Further, the Lipinski drug-likeness and admetSAR results also showed that Santalin A has good optimal oral bioavailability, non-carcinogenic and no toxic effect, suggesting all drug-like properties as compared to standard drug Rapamycin. Conclusion: Santalin-A, can be taken up as a potential lead compound for biological testing for developing a new drug for diabetic nephropathy, acting via mTOR signaling inhibition pathway.
P. Shree, D. Yadav, V. K. Singh, R. Chaube and Y. B. Tripathi *
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
28 June 2018
06 September 2018
15 September 2018
01 March 2019