Abstract
Sphingosine1-Phosphate Receptor1(S1PR1) a G protein-coupled receptor is critically involved in the trafficking of peripheral T-Lymphocyte into the Central Nervous System (CNS) leading to Remitting type of Multiple Sclerosis (RSMS). In the present scenario, the long-term benefits of the current immunomodulator against RSMS that bind specifically to S1PR1preventing the upward movement of lymphocytes toward CNS are uncertain due to the undesirable side effects. Therefore, in this paper, the author aims to screen derivatives of known immunomodulators used in Multiple Sclerosis (MS) treatment that binds specifically with S1PR1 receptor with better affinity and pharmacological properties than their parental compound. In this context, two promising analogs were screened namely CID_11623444 (L7A) and CID_445354 (RTL) of mitoxantrone and fingolimod, respectively that showed better pharmacokinetic properties, immunomodulatory activity, BBB permeability and affinity for S1PR1 receptors than their corresponding parental immunomodulator compound. Moreover, both the analogs were found to be specific inhibitors of S1PR1receptor by Baell and Holloway method. Therefore, based on the results it can be proposed that chemical analogs CID_11623444 and CID_445354 are useful lead molecules which may slow the progression of Multiple Sclerosis (MS) with greater efficacy and minimum side effects. (C) 2019 The Authors. Published by IASE.