Design, Synthesis, Bioactivity Analyses, and Molecular Docking Study of Triazine-Tyrosine Based Derivatives as Drugs like Fingolimod for Treatment of Multiple Sclerosis

Abstract

In this study, different heterocyclic entities consisting of tyrosine amino acid and triazine ring were designed based on the structure of fingolimod, the first oral drug for multiple sclerosis (MS). Interaction of these compounds with S1P1 and S1P3, as two involving targets for fingolimod, was evaluated utilizing molecular docking and then the designed compounds were synthesized and evaluated in the terms of red blood cell and T-lymphocyte depletion in comparison to fingolimod. The 4-aminopyridine substituted derivative (8a) showed low binding energy with the active site of S1P1 (−9.4 kcal/mol) and higher binding energy (−5.87 kcal/mol) with the active site of S1P3. Also, in pharmacological studies, this compound was able to reduce white blood cells better than fingolimod and did not show destructive effects on red blood cells, unlike fingolimod.